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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.
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Surtos de Doenças , Vigilância de Evento Sentinela , Febre Amarela , Uganda/epidemiologia , Humanos , Febre Amarela/epidemiologia , Febre Amarela/diagnósticoRESUMO
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.
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Surtos de Doenças , Humanos , Uganda/epidemiologia , Feminino , Masculino , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/diagnóstico , Adulto , Sudão/epidemiologia , Vigilância da População/métodos , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/diagnósticoRESUMO
Introduction: on March 21, 2020, the first case of COVID-19 was confirmed in Uganda. A total lockdown was initiated on March 30 which was gradually lifted May 5-June 30. On March 25, a toll-free call center was organized at the Kampala Capital City Authority to respond to public concerns about COVID-19 and the lockdown. We documented the set-up and use of the call center and analyzed key concerns raised by the public. Methods: two hotlines were established and disseminated through media platforms in Greater Kampala. The call center was open 24 hours a day and 7 days a week. We abstracted data on incoming calls from March 25 to June 30, 2020. We summarized call data into categories and conducted descriptive analyses of public concerns raised during the lockdown. Results: among 10,167 calls, two-thirds (6,578; 64.7%) involved access to health services, 1,565 (15.4%) were about social services, and 1,375 (13.5%) involved COVID-19-related issues. Approximately one-third (2,152; 32.7%) of calls about access to health services were requests for ambulances for patients with non-COVID-19-related emergencies. About three-quarters of calls about social services were requests for food and relief items (1,184; 75.7%). Half of the calls about COVID-19 (730; 53.1%) sought disease-related information. Conclusion: the toll-free call center was used by the public during the COVID-19 lockdown in Kampala. Callers were more concerned about access to essential health services, non-related to COVID-19 disease. It is important to plan for continuity of essential services before a public health emergency-related lockdown.
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COVID-19 , Call Centers , Acessibilidade aos Serviços de Saúde , Humanos , Uganda/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Call Centers/estatística & dados numéricos , Linhas Diretas/estatística & dados numéricos , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Controle de Doenças Transmissíveis/métodosRESUMO
INTRODUCTION: Early during the COVID-19 outbreak, various approaches were utilized to prevent COVID-19 introductions from incoming airport travellers. However, the costs and effectiveness of airport-specific interventions have not been evaluated. METHODS: We evaluated policy options for COVID-19-specific interventions at Entebbe International Airport for costs and impact on COVID-19 case counts, we took the government payer perspective. Policy options included; (1)no screening, testing, or mandatory quarantine for any incoming traveller; (2)mandatory symptom screening for all incoming travellers with RT-PCR testing only for the symptomatic and isolation of positives; and (3)mandatory 14-day quarantine and one-time testing for all, with 10-day isolation of persons testing positive. We calculated incremental cost-effectiveness ratios (ICERs) in US$ per additional case averted. RESULTS: Expected costs per incoming traveller were $0 (Option 1), $19 (Option 2), and $766 (Option 3). ICERs per case averted were $257 for Option 2 (which averted 4,948 cases), and $10,139 for Option 3 (which averted 5,097 cases) compared with Option I. Two-week costs were $0 for Option 1, $1,271,431 Option 2, and $51,684,999 Option 3. The per-case ICER decreased with increase in prevalence. The cost-effectiveness of our interventions was modestly sensitive to the prevalence of COVID-19, diagnostic test sensitivity, and testing costs. CONCLUSION: Screening all incoming travellers, testing symptomatic persons, and isolating positives (Option 2) was the most cost-effective option. A higher COVID-19 prevalence among incoming travellers increased cost-effectiveness of airport-specific interventions. This model could be used to evaluate prevention options at the airport for COVID-19 and other infectious diseases with similar requirements for control.
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BACKGROUND: Individuals living in communities with poor access to healthcare may be unaware of their high blood pressure (BP). While the use of community health workers (CHWs) can address gaps in human resources for health, CHWs in Uganda have not been used previously for BP screening and management. We report the results of an initiative to train CHWs to evaluate BP and to administer group-based education in Kalangala and Buvuma Island Districts of Lake Victoria, Uganda. METHODS: We randomly selected 42 of 212 villages. We trained CHWs based in island districts on measuring BP. CHWs visited all households in the selected villages and invited all adults ≥ 18 years to be screened for high BP. We used the World Health Organization's STEPwise tool to collect data on demographic and behavioral characteristics and BP measurements. High blood pressure was defined as systolic BP (SBP) ≥ 140 mm Hg and/or diastolic BP (DBP) ≥ 90 mm Hg over three readings. CHWs created and led fortnight support groups for individuals identified with high blood pressure at baseline. At each group meeting, CHWs re-measured BP and administered an intervention package, which included self-management and lifestyle education to participants. The paired t-test was used to compare mean values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after the intervention. Generalized estimating equations (GEE) were used to model longitudinal changes in BP. RESULTS: We trained 84 CHWs to measure BP and deliver the intervention package. Among 2,016 community members, 570 (28.3%) had high blood pressure; of these, 63 (11.1%) had a previous diagnosis of hypertension. The comparison of SBP and DBP before and after the intervention revealed significant reductions in mean SBP from 158mmHg (SD = 29.8) to 149 mmHg (SD = 29.8) (p < 0.001) and mean DBP from 97mmHg (SD = 14.3) to 92mmHg (p < 0.001). GEE showed decreases of -1.133 (SBP) and - 0.543 mmHg (DBP)/fortnight. CONCLUSION: High BP was common but previously undiagnosed. The CHW-led group-based self-management and education for controlling high BP was effective in the island districts in Uganda. Scaling up the intervention in other hard-to-reach districts could improve control of high BP on a large scale.
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Agentes Comunitários de Saúde , Hipertensão , Humanos , Uganda/epidemiologia , Agentes Comunitários de Saúde/educação , Feminino , Masculino , Adulto , Hipertensão/terapia , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Idoso , Educação em Saúde/métodos , Pressão Sanguínea/fisiologiaRESUMO
BACKGROUND: Uganda Ministry of Health (MOH) recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEI) and immediate return of results. WHO recommends initiating antiretroviral therapy (ART) ≤ 7 days from HIV diagnosis. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 130 facilities in 2020. We assessed results turnaround time and ART linkage pre-POC and during POC testing. METHODS: We evaluated EID register data for HEI at 10 health facilities with POC and EID testing volume of ≥ 12 infants/month from 2018 to 2021. We abstracted data for 12 months before and after POC testing rollout and compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon, and log-rank tests. RESULTS: Data for 4.004 HEI were abstracted, of which 1.685 (42%) were from the pre-POC period and 2.319 (58%) were from the period during POC; 3.773 (94%) had a first EID test (pre-POC: 1.649 [44%]; during POC: 2.124 [56%]). Median age at sample collection was 44 (IQR 38-51) days pre-POC and 42 (IQR 33-50) days during POC (p < 0.001). Among 3.773 HEI tested, 3.678 (97%) had test results. HIV-positive infants' (n = 69) median age at sample collection was 94 (IQR 43-124) days pre-POC and 125 (IQR 74-206) days during POC (p = 0.04). HIV positivity rate was 1.6% (27/1.617) pre-POC and 2.0% (42/2.061) during POC (p = 0.43). For all infants, median days from sample collection to results receipt by infants' caregivers was 28 (IQR 14-52) pre-POC and 1 (IQR 0-25) during POC (p < 0.001); among HIV-positive infants, median days were 23 (IQR 7-30) pre-POC and 0 (0-3) during POC (p < 0.001). Pre-POC, 4% (1/23) HIV-positive infants started ART on the sample collection day compared to 33% (12/37) during POC (p < 0.001); ART linkage ≤ 7 days from HIV diagnosis was 74% (17/23) pre-POC and 95% (35/37) during POC (p < 0.001). CONCLUSION: POC testing improved EID results turnaround time and ART initiation for HIV-positive infants. While POC testing expansion could further improve ART linkage and loss to follow-up, there is need to explore barriers around same-day ART initiation for infants receiving POC testing.
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Diagnóstico Precoce , Infecções por HIV , Testes Imediatos , Humanos , Uganda/epidemiologia , Lactente , Infecções por HIV/tratamento farmacológico , Infecções por HIV/diagnóstico , Feminino , Recém-Nascido , Masculino , Fármacos Anti-HIV/uso terapêutico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Teste de HIV/estatística & dados numéricos , Antirretrovirais/uso terapêuticoRESUMO
BACKGROUND: In 2022, an Ebola disease outbreak caused by Sudan virus (SUDV) occurred in Uganda, primarily affecting Mubende and Kassanda districts. We determined risk factors for SUDV infection among household members (HHM) of cases. METHODS: We conducted a case-control and retrospective cohort study in January 2023. Cases were RT-PCR-confirmed SUDV infection in residents of Mubende or Kassanda districts during the outbreak. Case-households housed a symptomatic, primary case-patient for ≥ 24 h and had ≥ 1 secondary case-patient with onset < 2 weeks after their last exposure to the primary case-patient. Control households housed a case-patient and other HHM but no secondary cases. A risk factor questionnaire was administered to the primary case-patient or another adult who lived at home while the primary case-patient was ill. We conducted a retrospective cohort study among case-household members and categorized their interactions with primary case-patients during their illnesses as none, minimal, indirect, and direct contact. We conducted logistic regression to explore associations between exposures and case-household status, and Poisson regression to identify risk factors for SUDV infection among HHM. RESULTS: Case- and control-households had similar median sizes. Among 19 case-households and 51 control households, primary case-patient death (adjusted odds ratio [ORadj] = 7.6, 95% CI 1.4-41) and ≥ 2 household bedrooms (ORadj=0.19, 95% CI 0.056-0.71) were associated with case-household status. In the cohort of 76 case-HHM, 44 (58%) were tested for SUDV < 2 weeks from their last contact with the primary case-patient; 29 (38%) were positive. Being aged ≥ 18 years (adjusted risk ratio [aRRadj] = 1.9, 95%CI: 1.01-3.7) and having direct or indirect contact with the primary case-patient (aRRadj=3.2, 95%CI: 1.1-9.7) compared to minimal or no contact increased risk of Sudan virus disease (SVD). Access to a handwashing facility decreased risk (aRRadj=0.52, 95%CI: 0.31-0.88). CONCLUSION: Direct contact, particularly providing nursing care for and sharing sleeping space with SVD patients, increased infection risk among HHM. Risk assessments during contact tracing may provide evidence to justify closer monitoring of some HHM. Health messaging should highlight the risk of sharing sleeping spaces and providing nursing care for persons with Ebola disease symptoms and emphasize hand hygiene to aid early case identification and reduce transmission.
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Surtos de Doenças , Características da Família , Doença pelo Vírus Ebola , Humanos , Uganda/epidemiologia , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/transmissão , Fatores de Risco , Masculino , Adulto , Feminino , Estudos Retrospectivos , Estudos de Casos e Controles , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Criança , Pré-Escolar , Ebolavirus , LactenteRESUMO
The precise anatomical degree of brain X chromosome inactivation (XCI) that is sufficient to alter X-linked disorders in females is unclear. Here, we quantify whole-brain XCI at single-cell resolution to discover a prevalent activation ratio of maternal to paternal X at 60:40 across all divisions of the adult brain. This modest, non-random XCI influences X-linked disease penetrance: maternal transmission of the fragile X mental retardation 1 (Fmr1)-knockout (KO) allele confers 55% of total brain cells with mutant X-active, which is sufficient for behavioral penetrance, while 40% produced from paternal transmission is tolerated. Local XCI mosaicism within affected maternal Fmr1-KO mice further specifies sensorimotor versus social anxiety phenotypes depending on which distinct brain circuitry is most affected, with only a 50%-55% mutant X-active threshold determining penetrance. Thus, our results define a model of X-linked disease penetrance in females whereby distributed XCI among single cells populating brain circuitries can regulate the behavioral penetrance of an X-linked mutation.
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Encéfalo , Camundongos Knockout , Penetrância , Inativação do Cromossomo X , Inativação do Cromossomo X/genética , Animais , Feminino , Camundongos , Encéfalo/metabolismo , Masculino , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Comportamento Animal , Camundongos Endogâmicos C57BL , Mosaicismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologiaRESUMO
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.
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Surtos de Doenças , Doença pelo Vírus Ebola , Humanos , Uganda/epidemiologia , Masculino , Feminino , Adulto , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Pessoa de Meia-Idade , Adulto Jovem , Tempo para o Tratamento , Adolescente , Sudão/epidemiologia , Fatores de Tempo , Isolamento de PacientesRESUMO
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.
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Ebolavirus , Doença pelo Vírus Ebola , Humanos , Busca de Comunicante , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Uganda/epidemiologia , Surtos de DoençasRESUMO
HIV infection is associated with poor maternal health outcomes. In 2016, the maternal mortality ratio (MMR) in Uganda was 336/100,000, and the neonatal mortality rate (NMR) was 19/1,000. Saving Mothers, Giving Life (SMGL) was a five-year maternal and neonatal health strengthening initiative launched in 2012 in Uganda. We extracted maternal and neonatal data for 2015-2016 from the initiative's population-based mortality surveillance system in 123 health facilities in Western Uganda. We collected data on the facilities, HIV status, antiretroviral drug (ARV) use, death, birth weight, delivery type, parity, Apgar scores, and complications. We compared mother and baby outcomes between HIV-positive or HIV-negative, computed risk ratios (RR) for adverse outcomes, and used the chi-square to test for significance in differences observed. Among 116,066 pregnant women who attended and gave birth at SMGL-implementing facilities during 2015-2016, 8,307 (7.7%) were HIV-positive, of whom 7,809 (94%) used antiretroviral drugs (ARVs) at the time of delivery. During birth, 23,993 (21%) women experienced ≥1 complications. Neonate Apgar scores <7 (8.8%) and maternal haemorrhage during birth (1.6%) were the most common outcomes. Overall facility MMR was 258/100,000 and NMR was 7.6/1,000. HIV infection increased risk of maternal death (RR = 3.6, 95% Confidence Interval (CI) = 2.4-5.5), maternal sepsis (RR = 2.1, 95% CI = 1.3-3.3), and infant birth weight <2,500g (RR = 1.2, 95% CI = 1.1-1.3), but was protective against maternal complications (RR = 0.92, 95% CI = 0.87-0.97) and perinatal death (RR = 0.78, 95% CI = 0.68-0.89). Among the HIV-positive, ARV non-use increased risk of maternal death (RR = 15, 95% CI = 7.1-31) and perinatal death (RR = 2.3, 95% CI = 1.6-3.4). SMGL reduced facility MMR and NMR below national rates. HIV-infection was associated with maternal sepsis and death. Failure to use ARVs among women living with HIV increased the risk of maternal and perinatal death. Use of the SMGL approach and complementary interventions that further strengthen HIV care, may continue to reduce MMR and NMR.
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BACKGROUND: Malaria outbreaks are detected by applying the World Health Organization (WHO)-recommended thresholds (the less sensitive 75th percentile or mean + 2 standard deviations [2SD] for medium-to high-transmission areas, and the more sensitive cumulative sum [C-SUM] method for low and very low-transmission areas). During 2022, > 50% of districts in Uganda were in an epidemic mode according to the 75th percentile method used, resulting in a need to restrict national response to districts with the highest rates of complicated malaria. The three threshold approaches were evaluated to compare their outbreak-signaling outputs and help identify prioritization approaches and method appropriateness across Uganda. METHODS: The three methods were applied as well as adjusted approaches (85th percentile and C-SUM + 2SD) for all weeks in 2022 for 16 districts with good reporting rates ( ≥ 80%). Districts were selected from regions originally categorized as very low, low, medium, and high transmission; district thresholds were calculated based on 2017-2021 data and re-categorized them for this analysis. RESULTS: Using district-level data to categorize transmission levels resulted in re-categorization of 8/16 districts from their original transmission level categories. In all districts, more outbreak weeks were detected by the 75th percentile than the mean + 2SD method (p < 0.001). For all 9 very low or low-transmission districts, the number of outbreak weeks detected by C-SUM were similar to those detected by the 75th percentile. On adjustment of the 75th percentile method to the 85th percentile, there was no significant difference in the number of outbreak weeks detected for medium and low transmission districts. The number of outbreak weeks detected by C-SUM + 2SD was similar to those detected by the mean + 2SD method for all districts across all transmission intensities. CONCLUSION: District data may be more appropriate than regional data to categorize malaria transmission and choose epidemic threshold approaches. The 75th percentile method, meant for medium- to high-transmission areas, was as sensitive as C-SUM for low- and very low-transmission areas. For medium and high-transmission areas, more outbreak weeks were detected with the 75th percentile than the mean + 2SD method. Using the 75th percentile method for outbreak detection in all areas and the mean + 2SD for prioritization of medium- and high-transmission areas in response may be helpful.
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Epidemias , Malária , Humanos , Uganda/epidemiologia , Surtos de Doenças , Malária/epidemiologiaRESUMO
The Allen Mouse Brain Connectivity Atlas consists of anterograde tracing experiments targeting diverse structures and classes of projecting neurons. Beyond regional anterograde tracing done in C57BL/6 wild-type mice, a large fraction of experiments are performed using transgenic Cre-lines. This allows access to cell-class-specific whole-brain connectivity information, with class defined by the transgenic lines. However, even though the number of experiments is large, it does not come close to covering all existing cell classes in every area where they exist. Here, we study how much we can fill in these gaps and estimate the cell-class-specific connectivity function given the simplifying assumptions that nearby voxels have smoothly varying projections, but that these projection tensors can change sharply depending on the region and class of the projecting cells. This paper describes the conversion of Cre-line tracer experiments into class-specific connectivity matrices representing the connection strengths between source and target structures. We introduce and validate a novel statistical model for creation of connectivity matrices. We extend the Nadaraya-Watson kernel learning method that we previously used to fill in spatial gaps to also fill in gaps in cell-class connectivity information. To do this, we construct a "cell-class space" based on class-specific averaged regionalized projections and combine smoothing in 3D space as well as in this abstract space to share information between similar neuron classes. Using this method, we construct a set of connectivity matrices using multiple levels of resolution at which discontinuities in connectivity are assumed. We show that the connectivities obtained from this model display expected cell-type- and structure-specific connectivities. We also show that the wild-type connectivity matrix can be factored using a sparse set of factors, and analyze the informativeness of this latent variable model.
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In the hall of animal oddities, the reindeer (Rangifer tarandus) is the only mammal with a color-shifting tapetum lucidum and the only ruminant with a lichen-dominated diet. These puzzling traits coexist with yet another enigma--ocular media that transmit up to 60% of ultraviolet (UV) light, enough to excite the cones responsible for color vision. It is unclear why any day-active circum-Arctic mammal would benefit from UV visual sensitivity, but it could improve detection of UV-absorbing lichens against a background of UV-reflecting snows, especially during the extended twilight hours of winter. To explore this idea and advance our understanding of reindeer visual ecology, we recorded the reflectance spectra of several ground-growing (terricolous), shrubby (fruticose) lichens in the diets of reindeer living in Cairngorms National Park, Scotland.
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BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that can cause severe haemorrhagic fevers in humans and high mortality rates and abortions in livestock. On 10 December 2020, the Uganda Ministry of Health was notified of the death of a 25-year-old male who tested RVF-positive by reverse-transcription polymerase chain reaction (RT-PCR) at the Uganda Virus Research Institute. We investigated to determine the scope of the outbreak, identify exposure factors, and institute control measures. METHODS: A suspected case was acute-onset fever (or axillary temperature > 37.5 °C) and ≥ 2 of: headache, muscle or joint pain, unexpected bleeding, and any gastroenteritis symptom in a resident of Sembabule District from 1 November to 31 December 2020. A confirmed case was the detection of RVF virus nucleic acid by RT-PCR or serum IgM antibodies detected by enzyme-linked immunosorbent assay (ELISA). A suspected animal case was livestock (cattle, sheep, goats) with any history of abortion. A confirmed animal case was the detection of anti-RVF IgM antibodies by ELISA. We took blood samples from herdsmen who worked with the index case for RVF testing and conducted interviews to understand more about exposures and clinical characteristics. We reviewed medical records and conducted an active community search to identify additional suspects. Blood samples from animals on the index case's farm and two neighbouring farms were taken for RVF testing. RESULTS: The index case regularly drank raw cow milk. None of the seven herdsmen who worked with him nor his brother's wife had symptoms; however, a blood sample from one herdsman was positive for anti-RVF-specific IgM and IgG. Neither the index case nor the additional confirmed case-patient slaughtered or butchered any sick/dead animals nor handled abortus; however, some of the other herdsmen did report high-risk exposures to animal body fluids and drinking raw milk. Among 55 animal samples collected (2 males and 53 females), 29 (53%) were positive for anti-RVF-IgG. CONCLUSIONS: Two human RVF cases occurred in Sembabule District during December 2020, likely caused by close interaction between infected cattle and humans. A district-wide animal serosurvey, animal vaccination, and community education on infection prevention practices campaign could inform RVF exposures and reduce disease burden.
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Research suggests parental ability to recognise when their child has overweight is limited. It is hypothesised that recognition of child overweight/obesity is fundamental to its prevention, acting as a potential barrier to parental action to improve their child's health-related behaviours and/or help seeking. The purpose of this study was to investigate the efficacy of an intervention (MapMe) to improve parental ability to correctly categorise their child as having overweight one-month post-intervention, and reduce child body mass index (BMI) z-score 12 months post-intervention. MapMe consists of body image scales of known child BMI and information on the consequences of childhood overweight, associated health-related behaviours and sources of support. We conducted a three-arm (paper-based MapMe, web-based MapMe and control) randomised control trial in fifteen English local authority areas with parents/guardians of 4-5- and 10-11-year-old children. Parental categorisation of child weight status was assessed using the question 'How would you describe your child's weight at the moment?' Response options were: underweight, healthy weight, overweight, and very overweight. Child weight status and BMI z-scores were calculated using objectively measured height and weight data and UK90 clinical thresholds. There was no difference in the percentage of parents correctly categorising their child as having overweight/very overweight (n = 264: 41% control, 48% web-based, and 43% paper-based, p = 0.646). BMI z-scores were significantly reduced for the intervention group at 12 months post-intervention compared to controls (n = 338, mean difference in BMI z-score change -0.11 (95% CI -0.202 to -0.020, p = 0.017). MapMe was associated with a decrease in BMI z-score 12 months post-intervention, although there was no direct evidence of improved parental ability to correctly categorise child overweight status. Further work is needed to replicate these findings in a larger sample of children, investigate mechanisms of action, and determine the use of MapMe as a public health initiative.
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IMPORTANCE: Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks.
Assuntos
Surtos de Doenças , Ebolavirus , Variação Genética , Doença pelo Vírus Ebola , Humanos , Surtos de Doenças/estatística & dados numéricos , Ebolavirus/química , Ebolavirus/classificação , Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/transmissão , Doença pelo Vírus Ebola/virologia , Uganda/epidemiologia , Busca de ComunicanteRESUMO
Neurodegenerative tauopathies are hypothesized to propagate via brain networks. This is uncertain because we have lacked precise network resolution of pathology. We therefore developed whole-brain staining methods with anti-p-tau nanobodies and imaged in 3D PS19 tauopathy mice, which have pan-neuronal expression of full-length human tau containing the P301S mutation. We analyzed patterns of p-tau deposition across established brain networks at multiple ages, testing the relationship between structural connectivity and patterns of progressive pathology. We identified core regions with early tau deposition, and used network propagation modeling to determine the link between tau pathology and connectivity strength. We discovered a bias towards retrograde network-based propagation of tau. This novel approach establishes a fundamental role for brain networks in tau propagation, with implications for human disease.