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Daniel Legese Achalu,1 Foziya Getachew Mohammed,2 Mekonnen Teferi1 1Clinical Trial Directorate, Armauer Hansen Research Institute, Addis Ababa, Ethiopia; 2Knowledge Management Directorate, Armauer Hansen Research Institute, Addis Ababa, EthiopiaCorrespondence: Daniel Legese Achalu, Tel +251912750932, Email danigateline@gmail.comBackground: Since its launch as a standardized treatment for multidrug-resistant tuberculosis (MDR-TB) in Ethiopia in April 2018, the safety profile of the shorter injectable regimen under a programmatic setting has not been well studied. Thus, this study aimed to assess the status of adverse events in patients treated with a shorter injectable regimen in Ethiopia.Methods: This is a retrospective cohort study. Data were collected using a structured data abstraction form and analyzed using SPSS, version 25, both descriptively and analytically. Logistic regression was conducted to assess predictors, and Kaplan–Meier analysis was used to examine the time to AEs and survival experiences.Results: Of 256 patients, 245 (95.7%) were eligible for the study. Of 245, 107 (43.7%) patients experienced at least one AE. In total, 276 AE cases were observed out of which the most common were nausea/vomiting (20.3%), dyspepsia (18.1%), and ototoxicity (11.6%). Of 276 AEs, approximately 49 (17.8%) were serious. AEs led to drug discontinuation, dose modification, and regimen change in 29 (27%), 15 (14%) and 10 (9.3%) patients, respectively. Only 19.2% of 276 the overall AEs and 22.6% of 62 AE of special interest (AESI) were reported to the National Pharmacovigilance Center.Conclusion: Although the observed extent of AEs associated with the shorter regimen (SR) seemed to be moderate, it significantly influenced the treatment schemes and patient conditions. Reporting of AEs was low, irrespective of their severity and AESI. Therefore, strengthening the implementation of active drug safety monitoring and management is required.Keywords: adverse events, adverse event of special interest, drug resistant tuberculosis, injectable, serious adverse event and shorter regimen

Cara Lynn Kim,1 Ligia Maria Cruz Espinoza,1 Kirsten S Vannice,2 Birkneh Tilahun Tadesse,1,3,4 Ellis Owusu-Dabo,5 Raphaël Rakotozandrindrainy,6 Ilesh V Jani,7 Mekonnen Teferi,8 Abdramane Bassiahi Soura,9 Octavie Lunguya,10,11 A Duncan Steele,2 Florian Marks1,6,12,13 1International Vaccine Institute, Seoul, Republic of Korea; 2Enteric and Diarrheal Diseases, Bill & Melinda Gates Foundation, Seattle, WA, USA; 3Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; 4Center for Innovative Drug Development and Therapeutic Trials for Africa, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 5School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; 6University of Antananarivo, Antananarivo, Madagascar; 7Instituto Nacional de Saúde (INS), Maputo Province, Mozambique; 8Armauer Hansen Research Institute, Addis Ababa, Ethiopia; 9Institut Supérieur des Sciences de la Population, Université Joseph Ki-Zerbo de Ouagadougou, Ouagadougou, Burkina Faso; 10Department of Microbiology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; 11Department of Medical Biology, University Teaching Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo; 12Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK; 13Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, GermanyCorrespondence: Florian Marks, Tel +82-2-881-1133, Email fmarks@ivi.intAbstract: While typhoid fever has largely been eliminated in high-income regions which have developed modern water, sanitation, and hygiene facilities, it remains a significant public health burden resulting in morbidity and mortality among millions of individuals in resource-constrained settings. Prevention and control efforts are needed that integrate several high-impact interventions targeting facilities and infrastructure, including those addressing improvements in sanitation, access to safe water, and planned urbanization, together with parallel efforts directed at effective strategies for use of typhoid conjugate vaccines (TCV). The use of TCVs is a critical tool with the potential of having a rapid impact on typhoid fever disease burden; their introduction will also serve as an important strategy to combat evolving antimicrobial resistance to currently available typhoid fever treatments. Well-designed epidemiological surveillance studies play a critical role in establishing the need for, and monitoring the impact of, typhoid fever control and prevention strategies implemented by public health authorities. Here, we present a perspective based on a narrative review of the impact of typhoid fever on morbidity and mortality in sub-Saharan Africa and discuss ongoing surveillance activities and the role of vaccination in prevention and control efforts.Keywords: typhoid, burden, mortality, sub-Saharan Africa, conjugate-vaccine, antimicrobial resistance

Background: Tuberculosis (TB) causes oxidative stress in patients contracting it while antioxidant vitamins such as ascorbic acid (AA) demonstrated antimycobacterial (anti-MTB) effects. Ascorbate's anti-MTB effect in 7H9 media depended on high iron concentration. However, high iron concentration in vivo rather favored mycobacterial growth. Iron dynamics in TB infected macrophages is also complex making it difficult to extrapolate ascorbate's in vivo effect based on observations in 7H9 media. To address this issue, we assessed ascorbate's anti- MTB effect in human macrophage cell culture model. Methods: We collected 20 ml blood from HIV negative subjects, isolated Peripheral Blood Mononuclear Cells (PBMCs) and separated monocytes from the PBMCs. Monocytes were allowed to mature, were infected with Mycobacterium TB (MTB) and were incubated in RPMI plus autologous serum after adding different concentrations of ascorbate. Colony Forming Units (CFU) were counted and compared among cultures incubated with different ascorbate concentrations. Ascorbate's anti-MTB effect was also assessed in 7H9 media for comparison. Results: At concentrations of 10-1 mM, 1 mM and 10 mM, ascorbate reduced MTB CFU in cell culture model by 13%, 53% and 71% respectively while in 7H9 medium CFU reductions were 2.8%, 58.7% and 99.3% respectively. Conclusions: Despite low iron concentration in human cell culture, ascorbate showed dose dependent anti-MTB effect in the cell culture and hence ascorbate can be further investigated in clinical trials to assess its use as an adjunct to anti- TB drugs [ABSTRACT FROM AUTHOR]

Background: STREAM stage 2 showed that two bedaquiline-containing regimens (a 9-month all-oral regimen and a 6-month regimen with 8 weeks of aminoglycoside) had superior efficacy to a 9-month injectable-containing regimen for rifampicin-resistant tuberculosis up to 76 weeks after randomisation. Our objective in this follow-up analysis was to assess the durability of efficacy and safety, including mortality, at 132 weeks., Methods: We report the long-term outcomes from STREAM stage 2, a randomised, phase 3 non-inferiority (10% margin) trial in participants (aged ≥15 years) with rifampicin-resistant tuberculosis without fluoroquinolone or aminoglycoside resistance at 13 clinical sites in seven countries (Ethiopia, Georgia, India, Moldova, Mongolia, South Africa, and Uganda). Participants were randomly assigned 1:2:2:2 (via permuted blocks and stratified by site and HIV status plus CD4 cell count) to the 2011 WHO long regimen (terminated early), a 9-month control regimen, a 9-month oral regimen with bedaquiline (primary comparison), or a 6-month regimen with bedaquiline and 8 weeks of an injectable antituberculous drug. Participants and clinicians were aware of treatment-group assignments, but laboratory staff were masked. The primary outcome, reported previously, was favourable status (negative cultures for Mycobacterium tuberculosis without a preceding unfavourable outcome; any death, bacteriological failure or recurrence, and major treatment change were considered unfavourable) at week 76. Here we report efficacy outcomes at week 132, analysed in the modified intention-to-treat (mITT) population. Safety assessments continued to 132 weeks and were in all participants who received at least one dose of the study regimen. All comparisons used concurrently randomised participants. This trial is registered on ISRCTN (ISRCTN18148631) and is now completed., Findings: Between March 28, 2016, and Jan 28, 2020, 588 participants were randomly assigned to the long (n=32), control (n=202), oral (n=211), or 6-month (n=143) treatment regimens; 352 (60%) were male and 236 (40%) were female. Of the 556 participants on the three shorter regimens, 517 were included in the mITT population (187 in control group, 196 in oral group, and 134 in 6-month group) and 465 in the per-protocol analyses. Six additional participants had an unfavourable outcome that occurred between week 76 and the end of efficacy follow-up (one in control group, four in oral group, one in 6-month group). In the mITT population, the proportion of patients with an unfavourable outcome at the end of follow-up was 19·6% (95% CI 14·3 to 24·9) in the oral group and 29·3% (23·3 to 36·5) in the control group (-9·7 percentage points difference [95% CI -18·7 to -1·8]; p superiority =0·024). An estimated 9·8% (95% CI 4·6 to 14·9) of participants on the 6-month regimen had an unfavourable outcome, which was significantly lower than for those concurrently on the control regimen (32·5% [23·7 to 40·2]; p superiority <0·0001) or the oral regimen (23·8% [16·9 to 31·1]; p superiority =0·013). Few serious or severe adverse events were reported after week 76, with no indication of a difference between the regimens. At week 132, treatment-emergent hearing loss was recorded in significantly fewer participants on the oral regimen (7/205; 3%) than the control regimen (16/198; 8%; p=0.041); there was no significant difference in severe hearing loss between the oral regimen (6/139; 4%) and the 6-month regimen (5/143; 4%; p=0·72). Death rates were low: 1·01 (95% CI 0·48 to 2·12) per 100 person-years in participants allocated to bedaquiline (ie, oral and 6-month regimen, n=287) compared with 1·52 (0·63 to 3·66) in participants on the control regimen (n=140; p=0·49)., Interpretation: Both of the bedaquiline-containing regimens maintained superiority to the control regimen, without evidence of increased mortality, providing two additional evidence-based treatment options for patients; previous mortality concerns for bedaquiline were not substantiated., Funding: US Agency for International Development and Janssen Research & Development., Competing Interests: Declaration of interests MR sat on the South African Bedaquiline, Pretomanid and Linezolid Clinical Access Program data monitoring committee and the BEAT Tuberculosis Trial data monitoring committee. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Past research has shown that the bilateral dorsolateral prefrontal cortices (dlPFC) are implicated in both emotional processing as well as cognitive processing, 1,2,3 in addition to working memory 4, 5 . Exactly how these disparate processes interact with one another within the dlPFC is less understood. To explore this, we designed a task that looked at working memory performance during fMRI under both emotional and non-emotional conditions, and tested it in this preliminary report. Participants were asked to complete three tasks (letters, neutral images, emotional images) of the Sternberg Sorting Task under one of two trial conditions (sort or maintain). Regions of interest consisted of the left and right dlPFC as defined by brain masks based on NeuroSynth 6 . Results showed a significant main effect of the 'sort' condition on reaction speed for all three trial types, as well as a main effect of task type (letters) on accuracy. In addition, a significant interaction was found between trial type (sort) and task type (letters), but not for either of the picture tasks. Although preliminary, these results reveal a discrepancy between BOLD signal and behavioral data, with no significant difference in BOLD activity during image trials being displayed, despite longer response times for every condition. While these initial results show that the dlPFC is implicated in non-emotional cognitive processing, more research is needed to explain the lack of BOLD activation seen here for similar emotionally valanced tasks, possibly indicating involvement of other brain networks., Competing Interests: Disclosures: This project was supported in part by 2 NARSAD Young Investigator Grants from the Brain & Behavior Research Foundation (NLB: 2018, 2021); and by a K01 award K01MH121777 (NLB). The authors report no biomedical financial interests or potential conflicts of interest.

Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration., (© 2024. The Author(s).)

Objective: Transcranial magnetic stimulation (TMS) can efficiently and robustly modulate synaptic plasticity, but little is known about how TMS affects functional connectivity (rs-fMRI). Accordingly, this project characterized TMS-induced rsFC changes in depressed patients who received 3 days of left prefrontal intermittent theta burst stimulation (iTBS)., Methods: rs-fMRI was collected from 16 subjects before and after iTBS. Correlation matrices were constructed from the cleaned rs-fMRI data. Electric-field models were conducted and used to predict pre-post changes in rs-fMRI. Site by orientation heatmaps were created for vectors centered on the stimulation site and a control site (contralateral motor cortex)., Results: For the stimulation site, there was a clear relationship between both site and coil orientation, and connectivity changes. As distance from the stimulation site increased, prediction accuracy decreased. Similarly, as eccentricity from the optimal orientation increased, prediction accuracy decreased. The systematic effects described above were not apparent in the heatmap centered on the control site., Conclusions: These results suggest that rs-fMRI following iTBS changes systematically as a function of the distribution of electrical energy delivered from the TMS pulse, as represented by the e-field model., Significance: This finding lays the groundwork for future studies to individualize TMS targeting based on how predicted rs-fMRI changes might impact psychiatric symptoms., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: The injectable shorter multi-drug resistant tuberculosis (MDR-TB) regimen, has been reported to be less costly and more effective in the treatment of MDR-TB compared to the longer regimen. Ethiopia introduced the injectable shorter regimen (SR) in April 2018 following official recommendation by the World Health Organization (WHO) in 2016. While the WHO recommendation was based on evidence coming from extensive programmatic studies in some Asian and African countries, there is paucity of information on patient outcomes in the Ethiopian context. Thus, we aimed to assess the treatment outcomes and identify factors associated with the outcomes of MDR-TB patients on injectable SR., Methods: A multi-center facility-based retrospective cohort study was conducted in Ethiopia on 245 MDR-TB patients who were treated between April 2018 and March 2020. Data were collected from patients' medical records and analyzed using SPSS version 25. Descriptive statistics was used to summarize the results while inferential analysis was employed to investigate predictors of treatment outcomes and survival status., Results: A total of 245 patients were included in the study, with 129 (52.7%) of them being female. Median age of the patients was 27 (IQR: 21-33). The overall treatment success rate was 87.8%, with 156 (63.7%) cured and 59 (24.1%) patients who completed treatment. The unfavorable outcomes accounted for 12.2%, with 16 (6.5%) treatment failure, 8 (3.3%) death and 6 (2.4%) lost to follow up. Majority of the unfavorable outcomes occurred during the early phase of therapy, with median time to event of 1.8 months (95% CI: 0.99-2.69). The use of khat (a green leafy shrub abused for its stimulant like effect) and being diagnosed with MDR-TB than rifampicin resistant only, were identified as independent factors associated with unfavorable outcomes., Conclusion: The injectable SR for MDR-TB was found to have positive treatment outcomes in the context of programmatic management in Ethiopia., (© 2024. The Author(s).)

Introduction: Ethiopia is one of those countries with higher burden of community acquired pneumonia among its people, under five children are the members of society that are highly affected by pneumonia particularly Severe Community Acquired Pneumonia. However, there are limited studies on time to recovery and its predictors in under-five children and most of them are retrospective which fails to address important variables that affect the time to recovery. Therefore, the aim of this study was to estimate the median time to recovery and its predictors among under five children admitted to South Wollo zone public hospitals, North East Ethiopia., Methods: An institution-based prospective cohort study was conducted from March 10 to May 10, 2021, with 270 study subjects. A systematic random sampling technique was used. Data was collected by interview and chart review. The data were entered and analyzed using Epi Data version 3.1 and STATA version 14.0, respectively. Kaplan-Meier and Cox regression models were used to test the time and predictors of recovery from severe community-acquired pneumonia., Results: The overall incidence of recovery rate (95% confidence interval) from Severe Community-Acquired Pneumonia was 20.45(17.84-23.46) per 100 person days observation with median (IQR) time to recovery of [3, 5] days. The predictors of time to recovery from Severe Community-Acquired Pneumonia were having comorbidities on admission [AHR = 0.49 (95%CI: 0.32,0.75)], reaching hospitals after 5 days of onset of symptoms [AHR = 0.35 (95%CI: 0.20,0.60)], having Middle Upper Arm Circumference < = 12.5 cm [AHR = 0.21 (95%CI: 0.12,0.37)], the presence of smoker in the house [AHR = 0.21 (95%CI: 0.10,0.42)] and being not fully immunized for age [AHR = 0.35 (95%CI: 0.24,0.53)]., Conclusion and Recommendations: Generally the recovery time of children with Severe Community Acquired Pneumonia in the study area was within the recommended national standards. Due attention should be given to children with the identified predictors while treating them., (© 2024. The Author(s).)

Background: The worldwide increase in multidrug resistance is a major threat to public health. One particular concern is the presence of Escherichia coli strains that carry Extended-Spectrum β-Lactamase (ESBL) and Carbapenemase enzymes, which can make multiple antibiotics ineffective. This complicates treatment strategies and raises the risk of illness and death. The aim of this study was to isolate E. coli O157:H7, assess its susceptibility against antimicrobial agents, and determine the presence of ESBL and Carbapenemase production in stool samples collected from diarrheic patients in Shashemene, west Arsi, Ethiopia from July to November 2022., Methods: The samples were cultured McConkey Agar and E. coli were isolated and identified by standard biochemical tests using API 20E. E. coli O157:H7 was further identified using sorbitol McConkey Agar and antisera for O157 antigen test. The antimicrobial susceptibility test was performed using the Kirby-Bauer disc diffusion method using different antibiotics. Each identified isolate was screened and tested for phenotypical ESBL and Carbapenemase production using combined disc method and modified carbapenem inactivation method, respectively. Bivariant and multivariant analyses were employed using a logistic regression model for further analysis and were interpreted based on the odds ratio and level of statistical significance at a p-value <0.05 with 95% confidence interval., Results: E. coli O157:H7 strain was found from 9% (38/423) study participants. The majority of the participants [61.9% (262/423)] were males; and 19.1% (81/ 423) of the participants were under five children. Living in urban areas, having domestic animals, and ≥5 family size in the household were identified as statistically significant factors associated with E. coli O157:H7. Twenty-seven (71.1%) and 12 (31.6%) of the 38 E. coli O157:H7 isolates were phenotypically confirmed to be ESBL and carbapenemase producers, respectively. All isolates were resistant against Ampicillin, but sensitive to ciprofloxacin. High resistance to Ampicillin and Amoxicillin/Clavulanic acid was observed among the ESBL and carbapenemase producing isolates also. The extent of detection of multidrug resistant E. coli O157:H7 isolates against three or more classes of antimicrobial agents tested was alarmingly very high (84%)., Conclusion: The E. coli O157:H7 isolates in this study showed a significant resistance to certain antimicrobials that were tested. The level of ESBL and Carbapenemase production among these isolates was found to be quite high. We observed a high resistance to Ampicillin and Amoxicillin/Clavulanic acid among the ESBL and carbapenemase producing isolates. Ciprofloxacin was found to be the most effective drug against both the ESBL producers and nonproducers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ayalneh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Cholera is an acute infectious disease caused by ingestion of contaminated food or water with Vibrio cholerae. Cholera remains a global threat to public health and an indicator of inequity and lack of social development. The aim of this study was to assess the prevalence and antimicrobial susceptibility pattern of V. cholerae from cholera outbreak sites in Ethiopia., Methods: Across-sectional study was conducted from May 2022 to October 2023 across different regions in Ethiopia: Oromia National Regional State, Amhara National Regional State and Addis Ababa City Administration. A total of 415 fecal samples were collected from the three regions. Two milliliter fecal samples were collected from each study participants. The collected samples were cultured on Blood Agar, MacConkey Agar and Thiosulfate Citrate Bile Salt Sucrose Agar. A series of biochemical tests Oxidase test, String test, Motility, Indole, Citrate, Gas production, H 2 S production, Urease test were used to identify V. cholerae species. Both polyvalent and monovalent antisera were used for agglutination tests to identify and differentiate V. cholerae serogroup and serotypes. In addition, Kirby-Bauer Disk diffusion antibiotic susceptibility test method was done. Data were registered in epi-enfo version 7 and analyzed by Statistical Package for Social Science version 25. Descriptive statistics were used to determine the prevalence of Vibrio cholerae. Logistic regression model was fitted and p-value < 0.05 was considered as statically significant., Results: The prevalence of V. cholerae in the fecal samples was 30.1%. Majority of the isolates were from Oromia National Regional State 43.2% (n = 54) followed by Amhara National Regional State 31.2% (n = 39) and Addis Ababa City Administration 25.6% (n = 32). Most of the V. cholerae isolates were O1 serogroups 90.4% (n = 113) and Ogawa serotypes 86.4% (n = 108). Majority of the isolates were susceptible to ciprofloxacin 100% (n = 125), tetracycline 72% (n = 90) and gentamycin 68% (n = 85). More than half of the isolates were resistant to trimethoprim-sulfamethoxazole 62.4% (n = 78) and ampicillin 56.8% (n = 71). In this study, participants unable to read and write were about four times more at risk for V. cholerae infection (AOR: 3.8, 95% CI: 1.07-13.33). In addition, consumption of river water were about three times more at risk for V. cholerae infection (AOR: 2.8, 95% CI: 1.08-7.08)., Conclusion: our study revealed a high prevalence of V. cholerae from fecal samples. The predominant serogroups and serotypes were O1 and Ogawa, respectively. Fortunately, the isolates showed susceptible to most tested antibiotics. Drinking water from river were the identified associated risk factor for V. cholerae infection. Protecting the community from drinking of river water and provision of safe and treated water could reduce cholera outbreaks in the study areas., (© 2024. The Author(s).)

Background: Refugees to the United States frequently have parasitic infections. If untreated, parasites can cause severe complications. The purpose of this study was to investigate the incidence, management, and outcomes of eosinophilia as a biomarker for parasites., Methods: We conducted a retrospective longitudinal chart review of consecutive refugees attending 3 refugee clinics in Rhode Island that manage the health care of all pediatric and adult refugees., Results: Among 812 refugees who met inclusion criteria, 147 (18.1%) had eosinophilia upon arrival and almost half had ≥1 symptom. The rates and severity of eosinophilia in those with predeparture presumptive treatment records who did (112/115, 97.4%) or did not (488/498, 98.0%) receive predeparture antiparasitic treatment were similar. All refugees with eosinophilia had ≥1 parasitic test in the United States. The most common attributable parasites were Schistosoma and Strongyloides stercoralis . Overall, parasites were detected in 63 (42.9%) of 147 refugees with eosinophilia by either stool testing, serology, or blood smear, but testing was inconsistent and likely underestimated true incidence. Only some of the identified parasites typically cause eosinophilia. Forty-five (30.6%) refugees with eosinophilia received antiparasitics in the United States. Of 81 (55.1%) individuals who had repeat blood tests, eosinophilia had resolved in 52 (64.2%). Five individuals (3.4%) had alternative diagnoses, including eczema, myelofibrosis, and drug allergy., Conclusions: Our findings support Centers for Disease Control and Prevention recommendations to screen for eosinophilia in newly arrived refugees. Follow-up after 3-6 months is critical to confirm resolution of residual eosinophilia, which frequently occurs after effective predeparture treatment or if eosinophilia persists, to diagnose active parasitic infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Healthcare seeking behavior (HSB) and community perception on cholera can influence its management. We conducted a cross-sectional survey to generate evidence on cholera associated HSB and disease perception in populations living in cholera hotspots in Ethiopia., Methods: A total of 870 randomly selected households (HHs) in Shashemene Town (ST) and Shashemene Woreda (SW) participated in our survey in January 2022., Results: Predominant HHs (91.0%; 792/870) responded "primary health center" as the nearest healthcare facility (HCF). Around 57.4% (247/430) of ST HHs traveled <30 minutes to the nearest HCF. In SW, 60.2% (265/440) of HHs travelled over 30 minutes and 25.9% (114/440) over 4 km. Two-thirds of all HHs paid

Background: Cholera outbreaks have afflicted Ethiopia, with nearly 100 000 cases and 1030 deaths reported from 2015 to 2023, emphasizing the critical need to understand water, sanitation, and hygiene (WaSH) risk factors., Methods: We conducted a cross-sectional household (HH) survey among 870 HHs in Shashemene Town and Shashemene Woreda, alongside extracting retrospective cholera case data from the Ethiopian Public Health Institute database. Relationships between WaSH and sociodemographic/economic-levels of HHs were examined. WaSH status and cholera attack rates (ARs) were described at kebele-level using geospatial mapping, and their association was statistically analyzed., Results: Access to basic drinking water, sanitation, and hygiene facilities was limited, with 67.5% (95% confidence interval, 64.4-70.6), 73.4% (70.3-76.3), and 30.3% (27.3-33.3) of HHs having access, respectively. Better WaSH practices were associated with urban residence (adjusted odds ratio, 1.7, [95% confidence interval, 1.1-2.7]), higher educational levels (2.7 [1.2-5.8]), and wealth (2.5 [1.6-4.0]). The association between cholera ARs and at least basic WaSH status was not statistically significant (multiple R2 = 0.13; P = .36), although localized effects were suggested for sanitation (Moran I = 0.22; P = .024)., Conclusions: Addressing gaps in WaSH access and hygiene practices is crucial for reducing cholera risk. Further analyses with meaningful covariates and increased sample sizes are necessary to understand the association between cholera AR and specific WaSH components., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cholera outbreaks in Ethiopia necessitate frequent mass oral cholera vaccine (OCV) campaigns. Despite this, there is a notable absence of a comprehensive summary of these campaigns. Understanding national OCV vaccination history is essential to design appropriate and effective cholera control strategies. Here, we aimed to retrospectively review all OCV vaccination campaigns conducted across Ethiopia between 2019 and 2023., Methods: The OCV request records from 2019 to October 2023 and vaccination campaign reports for the period from 2019 to December 2023 were retrospectively accessed from the Ethiopia Public Health Institute (EPHI) database. Descriptive analysis was conducted using the retrospective data collected., Results: From 2019 to October 2023, Ethiopian government requested 32 044 576 OCV doses (31 899 576 doses to global stockpile; 145 000 doses to outside of stockpile). Around 66.3% of requested doses were approved; of which 90.4% were received. Fifteen OCV campaigns (12 reactive and 3 pre-emptive) were conducted, including five two-dose campaigns with varying dose intervals and single-dose campaigns partially in 2019 and entirely in 2021, 2022 and 2023. Overall vaccine administrative coverage was high; except for Tigray region (41.8% in the 1st round; 2nd round didn't occur). The vaccine administrative coverage records were documented, but no OCV coverage survey data was available., Conclusions: This study represents the first comprehensive review of OCV campaigns in Ethiopia spanning the last five years. Its findings offer valuable insights into informing future cholera control strategies, underscoring the importance of monitoring and evaluation despite resource constraints. Addressing the limitations in coverage survey data availability is crucial for enhancing the efficacy of future campaigns., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cholera is a public health priority in Ethiopia. The Ethiopian National Cholera Plan elaborates a multi-year scheme of oral cholera vaccine (OCV) use. Aligned with this, a preemptive OCV campaign was conducted under our Ethiopia Cholera Control and Prevention project. Here, we present the OCV vaccination outcomes., Method: Cholera high-priority hotspots in the Oromia Region, Shashemene Town (ST) and Shashemene Woreda (SW), were selected. Four kebelles (Abosto, Alelu, Arada, and Awasho) in ST and 4 clusters (Faji Gole, Harabate, Toga, and Chabi) in SW were study sites with OCV areas nested within. A total of 40 000 and 60 000 people in ST and SW, respectively, were targeted for a 2-dose OCV (Euvichol-Plus) campaign in 11-15 May (first round [R1]) and 27-31 May (second round [R2]) 2022. Daily administrative OCV coverage and a coverage survey in 277 randomly selected households were conducted., Results: The administrative OCV coverage was high: 102.0% for R1 and 100.5% for R2 in ST and 99.1% (R1) and 100.0% (R1) in SW. The coverage survey showed 78.0% (95% confidence interval [CI]: 73.1-82.9) of household members with 2-dose OCV and 16.8% (95% CI: 12.4-21.3) with no OCV in ST; and 83.1% (95% CI: 79.6-86.5) with 2-dose OCV and 11.8% (95% CI: 8.8-14.8) with no OCV in SW. The 2-dose coverages in 1-4-, 5-14-, and ≥15-year age groups were 88.3% (95% CI: 70.6-96.1), 88.9% (95% CI: 82.1-95.7), and 71.3% (95% CI: 64.2-78.3), respectively, in ST and 78.2% (95% CI: 68.8-87.7), 91.0% (95% CI: 86.6-95.3), and 78.7% (95% CI: 73.2-84.1) in SW., Conclusions: High 2-dose OCV coverage was achieved. Cholera surveillance is needed to assess the vaccine impact and effectiveness., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Cholera remains a significant public health concern in Ethiopia. More than 15.9 million Ethiopians, constituting 15% of the total population, live in areas with a history of recurrent cholera outbreaks. The last 9 years of national cholera surveillance data show the country has been experiencing cholera outbreaks every year. The current cholera outbreak, starting in August 2022, has affected the entire country, with 841 reported cases and a 3.13% case fatality rate (CFR) in 2022, and >30 000 cases with nearly a 1.4% CFR in 2023. In line with "Ending Cholera-A Global Roadmap to 2030," the government of Ethiopia is committed to eliminate cholera in the country and has prepared its "National Cholera Elimination Plan (NCP): 2022-2028" with aims to achieve zero local transmission in cholera hotspot areas by 2028 and 90% fatality reduction from the recent (2020-2022) average of 1.8% CFR. The plan is multisectoral, has a clear coordination platform, contains all interventions with in-depth situational analysis, is concordant with existing plans and strategies, and is cascaded at the regional level and implemented with existing government and public structures. Nationwide, total 118 cholera hotspot woredas (districts) were identified, and a comprehensive situation analysis of the existing cholera outbreak response capacity was assessed. This multisectoral and multiyear NCP has forecasted around US$404 million budget estimates with >90% allocated to improving the country's water, sanitation, and hygiene (US$222 million; 55% of total NCP budget) and case management (US$149 million; 37%). The cholera vaccination strategy included in the NCP exhibited a 5-year oral cholera vaccine (OCV) introduction plan with 2 doses (30 604 889 doses) and single dose (3 031 266 doses) in selected cholera hotspot areas. However, its implementation is challenged due to a lack of financial support, inability to get the requested vaccine for targeted hotspot woredas (due to the current shortage of doses in the OCV global stockpile), recurrent cholera outbreaks, and high humanitarian needs in the country. It is recommended to have a sustainable financial mechanism to support implementation, follow the requested vaccine doses, and reorganize the planned coordination platform to foster the implementation., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The Ethiopian government has developed the multisectoral cholera elimination plan (NCP) with an aim of reducing cholera incidence and case fatality rate (CFR). To better understand and monitor the progress of this plan, a comprehensive review of national cholera epidemiology is needed., Methods: Reported data on cholera/acute watery diarrhea (AWD) cases in the past 20 years were extracted from the Ethiopian Public Health Institute and World Health Organization databases. Descriptive statistics, Pearson χ2, and logistic regression analyses were conducted., Results: From January 2001 to November 2023, a total of 215 205 cholera/AWD cases, 2355 deaths with a cumulative CFR of 1.10% (95% confidence interval [CI], 1.092-1.095), and a mean annual incidence rate of 8.9/100 000 (95% CI, 6.5-11.3) were reported. Two major upsurges of cholera epidemics were found in the last two decades with mean attack rate (AR) of 20.57/100 000 in 2006-2010 and 14.83/100 000 in 2016-2020. Another resurgence of outbreaks occured in 2021-2023 (mean AR, 8.63/100 000). In 2015-2023, 54.0% (53 990/99 945) of cases were aged 15-44 years. National cholera CFR (3.13% [95% CI: 2.1-4.5]) was the highest in 2022. The 2015-2023 cumulative cholera CFR was different across regions: Benishangul Gumuz (6.07%), Gambela (1.89%), Sidama (1.42%), Southern Nation, Nationalities, and Peoples' (1.34%), Oromia (1.10%), and Amhara (1.09%). Cholera/AWD patients in older adults (≥45 years), severe dehydration, peak rainy season (June-August), and outpatients were associated with higher risk of death., Conclusions: Cholera has been a public health problem in Ethiopia with case fatalities still above the global target. Case management needs to be improved particularly in outpatients and older populations. Outbreak preparedness should be rolled out well in advance of the typical rainy seasons. Significant investments are essential to advance the cholera surveillance system at healthcare setting and community level. Underlying factors of cholera deaths per areas should be further investigated to guide appropriate interventions to meet the NCP target by 2028., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Elevated arousal in anxiety is thought to affect attention control. To test this, we designed a visual short-term memory (VSTM) task to examine distractor suppression during periods of threat and no-threat. We hypothesized that threat would impair performance when subjects had to filter out large numbers of distractors. The VSTM task required subjects to attend to one array of squares while ignoring a separate array. The number of target and distractor squares varied systematically, with high (four squares) and low (two squares) target and distractor conditions. This study comprised two separate experiments. Experiment 1 used startle responses and white noise as to directly measure threat-induced anxiety. Experiment 2 used BOLD to measure brain responses. For Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. For Experiment 2, we found that accuracy was affected by threat, such that the distractor load negatively impacted accuracy only in the threat condition. We also found threat-related differences in parietal cortex activity. Overall, these findings suggest that threat affects distractor susceptibility, impairing filtering of distracting information. This effect is possibly mediated by hyperarousal of parietal cortex during threat., (Published by Oxford University Press 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Hypothermia is characterized by a drop in core body temperature of less than 36°C. It occurs frequently throughout the operating period and affects surgical patient outcomes differently in terms of morbidity and mortality. Because of coagulopathy, metabolic acidosis, multiple organ failure, hemodynamic instability, and infections, a core temperature below 34°C is strongly associated with mortality., Objective: This study aimed to assess the magnitude and associated factors of intraoperative hypothermia in pediatric patients undergoing elective surgery at the Ayder Comprehensive Specialized Hospital., Method: A prospective observational cross-sectional study was conducted on 399 pediatric patients undergoing elective surgery at Ayder Comprehensive Specialized Hospital in Tigray, Ethiopia, from 1 May 2023, to 30 July 2023. Participants in the study were selected by a systematic random sampling technique. The data collection procedure was chart review and intraoperative temperature measurement, and the collected data were analyzed by SPSS version 23. The independent variables were analyzed using binary and multi-logistic regression. The odds ratio, 95% CI, and p value of less than 0.05 were considered statistical significance., Result: The magnitude of intraoperative hypothermia was 52.9%. Neonate and infant [adjusted odds ratio (AOR): 6, 95% CI: 3.7, 9.8], (AOR=4.5, 95% CI: 2.9, 7) respectively, volume of fluid administered greater than half-liter [AOR: 4.37, (95% CI, 3, 6.4)], patients who underwent surgery during the morning [AOR: 5.3, (95% CI: 3.8, 7.4)], and duration of surgery and anesthesia greater than 120 minutes [AOR: 2.7, (95% CI, 1.8, 4)] and (AOR=3.4, 95% CI, 2.4, 4.9], respectively, were factors significantly associated with intraoperative hypothermia., Conclusion and Recommendation: This study revealed a high magnitude of intraoperative hypothermia among pediatric patients. Being neonates and infants, having a cold volume of IV fluid administered greater than half a liter, entering surgery during the morning, the duration of surgery, and the anesthesia time were significantly associated with intraoperative hypothermia. The authors would like to advise anesthetists to use warm intravenous fluids, calculate IV fluids, and maintain room temperature., Competing Interests: The authors declare that they have no competing interests.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model., Findings: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility., Interpretation: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices., Funding: The Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: With more than 1.2 million illnesses and 29,000 deaths in sub-Saharan Africa in 2017, typhoid fever continues to be a major public health problem. Effective control of the disease would benefit from an understanding of the subnational geospatial distribution of the disease incidence., Method: We collated records of the incidence rate of typhoid fever confirmed by culture of blood in Africa from 2000 to 2022. We estimated the typhoid incidence rate for sub-Saharan Africa on 20 km × 20 km grids by exploring the association with geospatial covariates representing access to improved water and sanitation, health conditions of the population, and environmental conditions., Results: We identified six published articles and one pre-print representing incidence rate estimates in 22 sites in 2000-2022. Estimated incidence rates showed geospatial variation at sub-national, national, and regional levels. The incidence rate was high in Western and Eastern African subregions followed by Southern and Middle African subregions. By age, the incidence rate was highest among 5-14 yo followed by 2-4 yo, > 14 yo, and 0-1 yo. When aggregated across all age classes and grids that comprise each country, predicted incidence rates ranged from 43.7 (95% confidence interval: 0.6 to 591.2) in Zimbabwe to 2,957.8 (95% CI: 20.8 to 4,245.2) in South Sudan per 100,000 person-years. Sub-national heterogeneity was evident with the coefficient of variation at the 20 km × 20 km grid-level ranging from 0.7 to 3.3 and was generally lower in high-incidence countries and widely varying in low-incidence countries., Conclusion: Our study provides estimates of 20 km × 20 km incidence rate of typhoid fever across sub-Saharan Africa based on data collected from 2000 through 2020. Increased understanding of the subnational geospatial variation of typhoid fever in Africa may inform more effective intervention programs by better targeting resources to heterogeneously disturbed disease risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)