Cross border population movements across three East African states: Implications for disease surveillance and response.

The frequent population movement across the five East African Countries poses risk of disease spread in the region. A clear understanding of population movement patterns is critical for informing cross-border disease control interventions. We assessed population mobility patterns across the borders of the East African states of Kenya, Uganda, and Rwanda. In November 2022, we conducted Focus Group Discussions (FGDs), Key Informant Interviews (KIIs), and participatory mapping. Participants were selected using purposive sampling and a topic guide used during interviews. Key informants included border districts (Uganda and Rwanda) and county health officials (Kenya). FGD participants were identified from border communities and travellers and these included truck drivers, commercial motorcyclists, and businesspersons. During KIIs and FGDs, we conducted participatory mapping using Population Connectivity Across Borders toolkits. Data were analysed using thematic analysis approach using Atlas ti 7 software. Different age groups travelled across borders for various reasons. Younger age groups travelled across the border for education, trade, social reasons, employment opportunities, agriculture and mining. While older age groups mainly travelled for healthcare and social reasons. Other common reasons for crossing the borders included religious and cultural matters. Respondents reported seasonal variations in the volume of travellers. Respondents reported using both official (4 Kenya-Uganda, 5 Rwanda-Uganda borders) and unofficial Points of Entry (PoEs) (14 Kenya-Uganda, 20 Uganda-Rwanda) for exit and entry movements on borders. Unofficial PoEs were preferred because they had fewer restrictions like the absence of health screening, and immigration and customs checks. Key destination points (points of interest) included: markets, health facilities, places of worship, education institutions, recreational facilities and business towns. Twenty-eight health facilities (10- Lwakhakha, Uganda, 10- Lwakhakha, Kenya, and 8- Cyanika, Uganda) along the borders were the most commonly visited by the travellers and border communities. Complex population movement and connectivity patterns were identified along the borders. These were used to guide cross-border disease surveillance and other border health strategies in the three countries. Findings were used to revise district response and preparedness plans by strengthening community-based surveillance in border communities.

The Role of Community Beliefs and Practices on the Spread of Ebola in Uganda, September 2022.

BACKGROUND: On September 20, 2022, Uganda declared an Sudan Virus Disease (SVD) outbreak in Mubende District. Another eight districts were infected September-November 2022. We examined how Ugandan community beliefs and practices spread Sudan Ebola Virus (SUDV) in 2022. METHODS: A qualitative study was conducted in Mubende, Kassanda, and Kyegegwa districts in February 2023. Nine focus group discussions and six key informant interviews were held. We investigated whether community beliefs and practices contributed to spreading Sudan Ebola Virus (SUDV). Interviews were recorded, translated, transcribed, and thematically analyzed. RESULTS: The community deaths, later found to be due to Sudan Virus Disease(SVD), were often attributed to witchcraft or poisoning. Key informants reported that SVD patients often sought traditional healers or spiritual leaders before or after formal healthcare failed. They also found that traditional healers treated SVD patients without precautions. Religious leaders praying for SVD patients and their symptomatic contacts, SVD patients hiding in friends' homes, and exhuming SVD patients from safe and dignified burials to allow traditional burials were other themes. CONCLUSION: Diversity in community beliefs and culture likely contributed to spreading the 2022 Ugandan SVD outbreak. Public health systems, traditional healers, and religious leaders can help Uganda control ebolavirus outbreaks by identifying socially acceptable and scientifically supported infection control methods.

Effect of cannabis use history on postoperative opioid utilization in lumbar fusion patients: an American retrospective study.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To examine the effect of cannabis use history on postoperative opioid utilization in patients undergoing one- to three-level lumbar fusion for degenerative spine disease. OVERVIEW OF LITERATURE: Strategies to minimize dosing and chronic opioid use are needed for spine surgery given their widespread prescription for postsurgical pain management. METHODS: In this database study, medical coding was used to identify patients who had undergone one- to three-level lumbar fusions between 2012 and 2021. Propensity score matching was used to create two equal cohorts with respect to cannabis use history. Opioid utilization rates (morphine milligram equivalents [MME]/day) and overuse rates at 6 months post-index procedure were assessed. All pvalues <0.05 were considered statistically significant. RESULTS: Following examination of 153,500 patient records, 1,216 patients were matched into cannabis user and non-cannabis user cohorts. Cannabis users had lower rates of opioid utilization compared to non-cannabis users as early as 2 months after fusion (47.7% vs. 41.1%, p <0.05), a relationship which persisted at 6 months (46.2% vs. 37.7%, p <0.01). Additionally, cannabis users had lower rates of high-dose opioid utilization (≥100 MME per day) during the initial 14-30 days following surgery (6.91% vs. 3.79%, p <0.05). CONCLUSIONS: Patients with a history of cannabis use were less likely to be using opioids as early as 2 months postoperatively and had lower rates of high-dose opioid utilization in the immediate postoperative period. Physicians operating on these patients should consider their cannabis use patterns to provide appropriate titration of pain medication over time.

Increasing trends of antibiotic resistance in Uganda: analysis of the national antimicrobial resistance surveillance data, 2018-2021.

BACKGROUND: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. METHODS: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. RESULTS: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), ß-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03). CONCLUSION: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."

Ebola disease outbreak caused by the Sudan virus in Uganda, 2022: a descriptive epidemiological study.

BACKGROUND: Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics. METHODS: For this descriptive study, cases were classified as suspected, probable, or confirmed using Ministry of Health case definitions. We investigated all reported cases to obtain data on case-patient demographics, exposures, and signs and symptoms, and identified transmission chains. We conducted a descriptive epidemiological study and also calculated basic reproduction number (Ro) estimates. FINDINGS: Between Aug 8 and Nov 27, 2022, 164 cases (142 confirmed, 22 probable) were identified from nine (6%) of 146 districts. The median age was 29 years (IQR 20-38), 95 (58%) of 164 patients were male, and 77 (47%) patients died. Symptom onsets ranged from Aug 8 to Nov 27, 2022. The case fatality rate was highest in children younger than 10 years (17 [74%] of 23 patients). Fever (135 [84%] of 160 patients), vomiting (93 [58%] patients), weakness (89 [56%] patients), and diarrhoea (81 [51%] patients) were the most common symptoms; bleeding was uncommon (21 [13%] patients). Before outbreak identification, most case-patients (26 [60%] of 43 patients) sought care at private health facilities. The median incubation was 6 days (IQR 5-8), and median time from onset to death was 10 days (7-23). Most early cases represented health-care-associated transmission (43 [26%] of 164 patients); most later cases represented household transmission (109 [66%]). Overall Ro was 1·25. INTERPRETATION: Despite delayed detection, the 2022 Sudan virus disease outbreak was rapidly controlled, possibly thanks to a low Ro. Children (aged <10 years) were at the highest risk of death, highlighting the need for targeted interventions to improve their outcomes during Ebola disease outbreaks. Initial care-seeking occurred at facilities outside the government system, showing a need to ensure that private and public facilities receive training to identify possible Ebola disease cases during an outbreak. Health-care-associated transmission in private health facilities drove the early outbreak, suggesting gaps in infection prevention and control. FUNDING: None.

Risk factors for death among children with severe malaria, Ivukula sub-county, Namutumba district, Eastern Uganda, september 2021-february 2022.

BACKGROUND: In February 2022, the Ministry of Health received reports of more than 100 child deaths from a 'strange disease' in Namutumba District over a period of 6 months from politicians through the media. Preliminary investigations by the district rapid response team confirmed the strange disease to be severe malaria. The scope of severe malaria deaths was investigated, associated factors identified, and recommendations made for control measures to inform early malaria treatment strategies in Namutumba District. METHODS: A retrospective study was conducted in March 2022 in the most affected subcounty (Ivukula Subcounty) involving cases and controls. A case was defined as a death with a positive malaria test, fever and any of the following: convulsions, difficulty breathing, yellowing of eyes or palms, tea-coloured urine, anaemia (evidenced by pale eyes or palms, or clinically-identified in medical records), loss of consciousness, or reduced urine output (very little or no urine in a day) in a child ≤ 12 years from September 2021 to February 2022 in Ivukula Subcounty, Namutumba District. Controls were survivors with the same signs and symptoms, recruited in a 2:1 ratio with cases. Cases and controls were actively searched using a door-to-door approach with the help of community health workers. Caretakers were interviewed to obtain data on signs and symptoms, socio-demographic information, health-seeking behaviours and health system risk factors. Drugs and bloodstock status information was obtained from health workers using an interview guide. Factors associated with death were identified using multivariate logistic regression and thematic analysis for qualitative data. RESULTS: Among 46 cases, 29 (63%) were < 5 years, and 23 (50%) were female. Death among children with severe malaria was significantly associated with treatment non-completion (aOR = 9.7, 95%CI 1.8-53) and inability to receive blood transfusion for anaemic patients (aOR = 7.1, (95%CI 1.4-36). Healthcare workers reported that inability to reach referral sites due to transport costs, stockouts of anti-malarials and blood products at health facilities, and absence of integrated community case management of childhood illnesses (iCCM) contributed to deaths among children with severe malaria. CONCLUSION: Lack of access to anti-malarial treatment and to blood transfusions among anaemic patients due to stockouts were associated with severe malaria deaths among children ≤ 12 years in Ivukula Subcounty. Recommendations made were: accurate quantification of anti-malarials for health facilities, offering transport support to severe patients referred to higher-level facilities, and increasing access to blood products. Activation of iCCM could facilitate public health efforts against severe malaria in the district.

Factors associated with severe pneumonia among children <5 years, Kasese District, Uganda: a case-control study, January-April 2023.

BACKGROUND: Pneumonia is one of the leading causes of infant mortality globally, particularly in sub-Saharan Africa. In Uganda, pneumonia was the fourth leading cause of death in children <5 years in 2018. Analysis of 2013-2022 data for children <5 years from the District Health Information System indicated a high incidence of severe pneumonia in Kasese District, Uganda. We investigated to identify factors associated with severe pneumonia among children <5 years in Kasese District to inform prevention and control strategies. METHODS: We conducted a 1:1 hospital-based case-control study among children aged 2-59 months presenting with pneumonia at five high-volume facilities in Kasese District from January to April 2023. A case was defined as pneumonia with ≥1 of the following danger signs: low oxygen saturation, central cyanosis, severe respiratory distress, feeding difficulties, altered consciousness, and convulsions. Controls were outpatient children aged 2-59 months with a diagnosis of non-severe pneumonia. We reviewed medical records at facilities and used an interviewer-administered questionnaire with caregivers to obtain information on socio-demographic and clinical characteristics. Logistic regression was used to identify factors associated with severe pneumonia. RESULTS: We enrolled 199 cases and 174 controls. The odds of severe pneumonia were higher among children with diarrhoea only (adjusted odds ratio [aOR] = 2.9, 95%CI: 1.7-4.9), or malaria and diarrhoea (aOR = 3.4, 95%CI: 2.0-5.9), than those without a co-existing illness at the time of pneumonia diagnosis. Not being exclusively breastfed for ≥ 6 months (aOR = 2.0, 95%CI: 1.1-3.3) and exposure to indoor air pollution from cooking combustion sources (aOR = 2.9, 95%CI: 1.8-4.7) increased odds of severe pneumonia. CONCLUSION: The findings highlight the significance of comorbidities, lack of exclusive breastfeeding, and exposure to indoor air pollution in the development of severe pneumonia. Promoting exclusive breastfeeding for ≥ 6 months and advocating for the use of clean energy sources, could mitigate morbidity attributable to severe pneumonia in the region.

Evaluation of the sentinel yellow fever surveillance system in Uganda, 2017-2022: strengths and weaknesses.

BACKGROUND: Uganda has a sentinel surveillance system in seven high-risk sites to monitor yellow fever (YF) patterns and detect outbreaks. We evaluated the performance of this system from 2017 to 2022. METHODS: We evaluated selected attributes, including timeliness (lags between different critical time points), external completeness (proportion of expected sentinel sites reporting ≥ 1 suspect case in the system annually), and internal completeness (proportion of reports with the minimum required data elements filled), using secondary data in the YF surveillance database from January 2017-July 2022. We conducted key informant interviews with stakeholders at health facility and national level to assess usefulness, flexibility, simplicity, and acceptability of the surveillance system. RESULTS: In total, 3,073 suspected and 15 confirmed YF cases were reported. The median time lag from sample collection to laboratory shipment was 37 days (IQR:21-54). External completeness was 76%; internal completeness was 65%. Stakeholders felt that the surveillance system was simple and acceptable, but were uncertain about flexibility. Most (71%) YF cases in previous outbreaks were detected through the sentinel surveillance system; data were used to inform interventions such as intensified YF vaccination. CONCLUSION: The YF sentinel surveillance system was useful in detecting outbreaks and informing public health action. Delays in case confirmation and incomplete data compromised its overall effectiveness and efficiency.

The Impact of Preoperative Spinal Injection Timing on the Postoperative Complications of Lumbar Fusion.

OBJECTIVE: To determine the impact of epidural spinal injections (ESIs) on postoperative surgical complications. METHODS: This retrospective all-payer database analysis identified 202,181 adult patients undergoing one- to three-level transforaminal lumbar interbody fusion (TLIF) from 2010 to 2020. A 1:1 exact matching on comorbidities and demographics was performed, creating 2 cohorts: 1) patients who received an ESI within 90 days of surgery and 2) patients who did not receive an ESI. The primary outcome was surgical complication rates between groups at 30 days postoperatively. For the secondary outcome, patients were stratified based on injection time before surgery: 1-30, 31-45, 46-60, 61-75, and 76-90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. The P value was set to 0.05 for the primary analysis, and the Bonferroni correction was utilized for the secondary outcome. RESULTS: Exact matching produced 12,491 pairs for analysis. Groups were well-matched on demographics, comorbidities, and fusion levels. The 30-day postoperative rates of surgical complications, hematomas, wound disruptions, or surgical site infections did not differ between groups (P > 0.05). The rate of cerebrospinal fluid (CSF) leak was increased in the ESI group (0.19% vs. 0.09%, P = 0.042). When temporally stratified, patients receiving an ESI within 30 days had significantly higher odds of CSF leak (odds ratio: 4.24, 95% confidence interval: 1.97-9.14). CONCLUSIONS: Patients who receive an ESI within 30 days of transforaminal lumbar interbody fusion are at an increased risk for CSF leak. While the incidence of CSF leak remains small, it may be advisable to avoid ESIs at least 30 days before surgery for certain patients.

Understanding the delay in identifying Sudan Virus Disease: gaps in integrated disease surveillance and response and community-based surveillance to detect viral hemorrhagic fever outbreaks in Uganda, September 2022.

BACKGROUND: Early detection of outbreaks requires robust surveillance and reporting at both community and health facility levels. Uganda implements Integrated Disease Surveillance and Response (IDSR) for priority diseases and uses the national District Health Information System (DHIS2) for reporting. However, investigations after the first case in the 2022 Uganda Sudan virus outbreak was confirmed on September 20, 2022 revealed many community deaths among persons with Ebola-like symptoms as far back as August. Most had sought care at private facilities. We explored possible gaps in surveillance that may have resulted in late detection of the Sudan virus disease (SVD) outbreak in Uganda. METHODS: Using a standardized tool, we evaluated core surveillance capacities at public and private health facilities at the hospital level and below in three sub-counties reporting the earliest SVD cases in the outbreak. Key informant interviews (KIIs) were conducted with 12 purposively-selected participants from the district local government. Focus group discussions (FGDs) were conducted with community members from six villages where early probable SVD cases were identified. KIIs and FGDs focused on experiences with SVD and Viral Hemorrhagic Fever (VHF) surveillance in the district. Thematic data analysis was used for qualitative data. RESULTS: Forty-six (85%) of 54 health facilities surveyed were privately-owned, among which 42 (91%) did not report to DHIS2 and 39 (85%) had no health worker trained on IDSR; both metrics were 100% in the eight public facilities. Weak community-based surveillance, poor private facility engagement, low suspicion index for VHF among health workers, inability of facilities to analyze and utilize surveillance data, lack of knowledge about to whom to report, funding constraints for surveillance activities, lack of IDSR training, and lack of all-cause mortality surveillance were identified as gaps potentially contributing to delayed outbreak detection. CONCLUSION: Both systemic and knowledge-related gaps in IDSR surveillance in SVD-affected districts contributed to the delayed detection of the 2022 Uganda SVD outbreak. Targeted interventions to address these gaps in both public and private facilities across Uganda could help avert similar situations in the future.

Understanding Glucagon Aggregation: In Silico Insights and Experimental Validation.

Peptide aggregation poses a significant challenge in biopharmaceutical development and neurodegenerative diseases. This study combines computational simulations and experimental validation to uncover the underlying mechanisms and countermeasures for the aggregation of glucagon, a peptide with a high tendency to aggregate. In silico simulations demonstrate that lactose and 2-hydroxypropyl-ß-cyclodextrin (2-HPßCD) influence glucagon aggregation differently: lactose stabilizes glucagon by increasing the α-helical content, while 2-HPßCD disrupts protein-protein interactions. According to the simulations, 2-HPßCD is particularly effective at preserving the monomeric form of glucagon. Experimental validation with microfluidic modulation spectroscopy (MMS) confirms these findings, showing that glucagon in the presence of 2-HPßCD remains structurally stable, supporting the antiaggregation effect of this excipient. This research provides essential insights into glucagon aggregation obtained through a new powerful tool for monitoring the critical properties of peptide aggregation, suggesting new strategies for addressing this challenge in therapeutic peptide development.

Sudan virus disease super-spreading, Uganda, 2022.

BACKGROUND: On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak. METHODS: In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases. RESULTS: Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data. CONCLUSION: Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events.

Time to care and factors influencing appropriate Sudan virus disease care among case patients in Uganda, September to November 2022.

OBJECTIVES: Early isolation and care for Ebola disease patients at Ebola Treatment Units (ETU) curb outbreak spread. We evaluated time to ETU entry and associated factors during the 2022 Sudan virus disease (SVD) outbreak in Uganda. METHODS: We included persons with RT-PCR-confirmed SVD with onset September 20-November 30, 2022. We categorized days from symptom onset to ETU entry ("delays") as short (≤2), moderate (3-5), and long (≥6); the latter two were "delayed isolation." We categorized symptom onset timing as "earlier" or "later," using October 15 as a cut-off. We assessed demographics, symptom onset timing, and awareness of contact status as predictors for delayed isolation. We explored reasons for early vs late isolation using key informant interviews. RESULTS: Among 118 case-patients, 25 (21%) had short, 43 (36%) moderate, and 50 (43%) long delays. Seventy-five (64%) had symptom onset later in the outbreak. Earlier symptom onset increased risk of delayed isolation (crude risk ratio = 1.8, 95% confidence interval (1.2-2.8]). Awareness of contact status and SVD symptoms, and belief that early treatment-seeking was lifesaving facilitated early care-seeking. Patients with long delays reported fear of ETUs and lack of transport as contributors. CONCLUSION: Delayed isolation was common early in the outbreak. Strong contact tracing and community engagement could expedite presentation to ETUs.

Performance and impact of contact tracing in the Sudan virus outbreak in Uganda, September 2022-January 2023.

BACKGROUND: Contact tracing (CT) is critical for ebolavirus outbreak response. Ideally, all new cases after the index case should be previously-known contacts (PKC) before their onset, and spend minimal time ill in the community. We assessed the impact of CT during the 2022 Sudan Virus Disease (SVD) outbreak in Uganda. METHODS: We collated anonymized data from the SVD case and contacts database to obtain and analyze data on CT performance indicators, comparing confirmed cases that were PKC and were not PKC (NPKC) before onset. We assessed the effect of being PKC on the number of people infected using Poisson regression. RESULTS: There were 3844 contacts of 142 confirmed cases (mean: 22 contacts/case). Forty-seven (33%) confirmed cases were PKC. PKCs had fewer median days from onset to isolation (4 vs 6; P<0.007) and laboratory confirmation (4 vs 7; P<0.001) than NPKC. Being a PKC vs NPKC reduced risk of transmitting infection by 84% (IRR=0.16, 95% CI 0.08-0.32). CONCLUSION: Contact identification was sub-optimal during the outbreak. However, CT reduced the time SVD cases spent in the community before isolation and the number of persons infected in Uganda. Approaches to improve contact tracing, especially contact listing, may improve control in future outbreaks.

Syndromic surveillance during 2022 Uganda Martyrs' commemoration.

Mass gatherings frequently include close, prolonged interactions between people, which presents opportunities for infectious disease transmission. Over 20,000 pilgrims gathered at Namugongo Catholic and Protestant shrines to commemorate 2022 Uganda Martyr's Day. We described syndromes suggestive of key priority diseases particularly COVID-19 and viral hemorrhagic fever (VHF) among visiting pilgrims during May 25-June 5, 2022. We conducted a survey among pilgrims at the catholic and protestant shrines based on signs and symptoms for key priority diseases: COVID-19 and VHF. A suspected COVID-19 case was defined as acute respiratory illness (temperature greater 37.5°C and at least one sign/symptom of respiratory infection such as cough or shortness of breath) whereas a suspected VHF case was defined as fever >37.5°C and unexplained bleeding among pilgrims who visited Namugongo Catholic and Protestant shrines from May 25 to June 5, 2022. Pilgrims were sampled systematically at entrances and demarcated zonal areas to participate in the survey. Additionally, we extracted secondary data on pilgrims who sought emergency medical services from Health Management Information System registers. Descriptive analysis was conducted to identify syndromes suggestive of key priority diseases. Among 1,350 pilgrims interviewed, 767 (57%) were female. The mean age was 37.9 (±17.9) years. Nearly all pilgrims 1,331 (98.6%) were Ugandans. A total of 236 (18%) reported ≥1 case definition symptom and 42 (3%) reported ≥2 symptoms. Thirty-nine (2.9%) were suspected COVID-19 cases and three (0.2%) were suspected VHF cases from different regions of Uganda. Among 5,582 pilgrims who sought medical care from tents, 628 (11.3%) had suspected COVID-19 and one had suspected VHF. Almost one in fifty pilgrims at the 2022 Uganda Martyrs' commemoration had at least one symptom of COVID-19 or VHF. Intensified syndromic surveillance and planned laboratory testing capacity at mass gatherings is important for early detection of public health emergencies that could stem from such events.

Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells.

Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.

Rubrospinal activation during asleep subthalamic nucleus deep brain stimulation: a false localizing sign. Illustrative case.

BACKGROUND: Deep brain stimulation (DBS) can be a life-changing intervention for patients with Parkinson's disease (PD), but its success is largely dependent on precise lead placement. The subthalamic nucleus (STN) is one of the most common surgical targets of DBS, but the close anatomical and physiological resemblance of the STN to the mediocaudal red nucleus renders these landmarks difficult to distinguish. OBSERVATIONS: We present an atypical case in which targeted localization of the STN resulted in symptoms pathognomonic of rubrospinal tract (RST) stimulation. A 79-year-old female with a 12-year history of right-hand resting tremor due to medically refractory PD presented for asleep bilateral STN-DBS surgery. Right STN intraoperative testing revealed left hand and elbow flexion contractures, initially suggestive of corticospinal tract activation, despite imaging studies demonstrating reasonable lead placement in the central dorsolateral STN. The lead was moved anteromedially near the medial border of the STN, but stimulation at this location revealed similar but more robust flexor hand and arm contractures, without any extraocular muscle involvement. Thus, activation of the RST was suspected. LESSONS: Isolated activation of the RST is possible during STN-DBS surgery. Its identification can help avoid false localization and suboptimal lead placement.

Stem Cell Implants: Emerging Innovation for Stroke Recovery.

Stroke is a debilitating neurovascular injury that those effects hundreds of thousands of Americans each year. Despite the high prevalence, disease morbidity and mortality, options for stroke intervention and rehabilitation are still limited. Stem cells have shown promise in stroke treatment due to their ability to self-renew and differentiate into different cell types. The primary sources of stem cells used today are bone marrow and fetal brain tissue, with mesenchymal stem cells, bone marrow stem cells and neural stem cells being particularly well-studied. By secreting therapeutic and neurogenic substances they are hypothesized to help foster recovery at the site of injury. Delivery mechanisms for stem cell therapy include intracerebral, intra-arterial, intraperitoneal, intravenous, intraventricular and intranasal routes with radiographic imaging now being used to monitor the progress of stem cell therapies. Stem cell implants have been found to be safe but optimal treatment strategies are still being established with several promising studies underway. Future efforts should continue to focus on improving efficacy, exploring alternative stem cell sources, enhancing migration capability and survival and educating stroke patients on the benefits and risks of stem cell therapy.

Innovation in Neurosurgery: Lessons Learned, Obstacles, and Potential Funding Sources.

Innovation is central to neurosurgery and has dramatically increased over the last twenty years. Although the specialty innovates as a whole, only 3-4.7% of practicing neurosurgeons hold patents. Various roadblocks to innovation impede this process such as lack of understanding, increasing regulatory complexity, and lack of funding. Newly emerging technologies allow us to understand how to innovate and how to learn from other medical specialties. By further understanding the process of innovation, and the funding that supports it, Neurosurgery can continue to hold innovation as one of its's central tenets.

Reduced C9ORF72 function exacerbates gain of toxicity from ALS/FTD-causing repeat expansion in C9orf72.

Hexanucleotide expansions in C9orf72, which encodes a predicted guanine exchange factor, are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although repeat expansion has been established to generate toxic products, mRNAs encoding the C9ORF72 protein are also reduced in affected individuals. In this study, we tested how C9ORF72 protein levels affected repeat-mediated toxicity. In somatic transgenic mice expressing 66 GGGGCC repeats, inactivation of one or both endogenous C9orf72 alleles provoked or accelerated, respectively, early death. In mice expressing a C9orf72 transgene with 450 repeats that did not encode the C9ORF72 protein, inactivation of one or both endogenous C9orf72 alleles exacerbated cognitive deficits, hippocampal neuron loss, glial activation and accumulation of dipeptide-repeat proteins from translation of repeat-containing RNAs. Reduced C9ORF72 was shown to suppress repeat-mediated elevation in autophagy. These efforts support a disease mechanism in ALS/FTD resulting from reduced C9ORF72, which can lead to autophagy deficits, synergizing with repeat-dependent gain of toxicity.