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1.
Cell ; 185(6): 995-1007.e18, 2022 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-35303429

RESUMEN

Several ebolaviruses cause outbreaks of severe disease. Vaccines and monoclonal antibody cocktails are available to treat Ebola virus (EBOV) infections, but not Sudan virus (SUDV) or other ebolaviruses. Current cocktails contain antibodies that cross-react with the secreted soluble glycoprotein (sGP) that absorbs virus-neutralizing antibodies. By sorting memory B cells from EBOV infection survivors, we isolated two broadly reactive anti-GP monoclonal antibodies, 1C3 and 1C11, that potently neutralize, protect rodents from disease, and lack sGP cross-reactivity. Both antibodies recognize quaternary epitopes in trimeric ebolavirus GP. 1C11 bridges adjacent protomers via the fusion loop. 1C3 has a tripartite epitope in the center of the trimer apex. One 1C3 antigen-binding fragment anchors simultaneously to the three receptor-binding sites in the GP trimer, and separate 1C3 paratope regions interact differently with identical residues on the three protomers. A cocktail of both antibodies completely protected nonhuman primates from EBOV and SUDV infections, indicating their potential clinical value.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Ebolavirus , Fiebre Hemorrágica Ebola , Animales , Epítopos , Glicoproteínas/química , Subunidades de Proteína
2.
J Virol ; 98(8): e0124223, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39012096

RESUMEN

Sudan ebolavirus (SUDV) is a member of the genus Ebolavirus (Family Filoviridae) and has caused sporadic outbreaks of Ebola disease (EBOD), or more specifically Sudan virus disease (SVD), with high mortality rates in Africa. Current vaccines and therapies that have been developed for filoviruses are almost all specific for Ebola virus (EBOV; of the species Zaire ebolavirus), and there is a current lack of therapeutics specific for SUDV. The recent SUDV outbreak in Uganda, which was distributed across multiple districts, including Kampala, a densely populated urban center, highlights the critical need for the development of novel SUDV-specific or pan-Ebola virus therapeutics. Previous work has characterized two monoclonal antibodies, FVM04 and CA45, which have neutralization capabilities against both EBOV and SUDV and have shown protective efficacy in animal challenge studies. Here, we expand upon this work, showing that treatment with a monoclonal antibody cocktail consisting of FVM04 and CA45 provides full protection against lethal SUDV infection in cynomolgus macaques. Studies that evaluate outcomes at late time points after infection, once clinical signs of illness are apparent, are vital for assessing the therapeutic efficacy of antibody therapeutics. We have shown that when treatment is initiated as late as 5 days after infection, with a second dose given on day 8, that treated groups showed few clinical signs or morbidity, with complete survival. This work provides further evidence that FVM04 and CA45 have strong therapeutic potential against SUDV and their development as a pan-Ebola virus therapeutic should be pursued. IMPORTANCE: There are currently no approved vaccines or therapeutics for Sudan virus, a filovirus which is highly related to Ebola virus and causes similar disease and outbreaks. In this study, a cocktail of two potent monoclonal antibodies that effectively neutralize Sudan virus was tested in a nonhuman primate model of Sudan virus disease. Treatment was highly effective, even when initiated as late as 5 days after infection, when clinical signs of infection were already evident. All treated animals showed complete recovery from infection, with little evidence of disease, while all animals that received a control treatment succumbed to infection within 8 days. The study further demonstrated the strong therapeutic potential of the antibody treatment and supported further development for use in Sudan virus outbreaks.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Ebolavirus , Fiebre Hemorrágica Ebola , Retraso del Tratamiento , Animales , Femenino , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Modelos Animales de Enfermedad , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Macaca fascicularis , Masculino
3.
J Infect Dis ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39126336

RESUMEN

BACKGROUND: Ebola (EBOV) and Sudan (SUDV) orthoebolaviruses are responsible for lethal haemorrhagic fever outbreaks in humans in Central and West Africa, and in apes that can be at the source of human outbreaks for EBOV. METHODS: To assess the risk of exposure to orthoebolaviruses through contact with non-human primates (NHP), we tested the presence of antibodies against different viral proteins with a microsphere-based multiplex immunoassay in a case-control study on bites from NHPs in forest areas from Cameroon (n=795), and in cross-sectional surveys from other rural populations (n=622) of the same country. RESULTS: Seroreactivities against at least two viral proteins were detected in 13% and 12% of the samples for EBOV and SUDV, respectively. Probability of seroreactivity was not associated with history of NHP bites, but was three times higher in Pygmies compared to Bantus. Although no neutralizing antibodies to EBOV and SUDV were detected in a selected series of highly reactive samples, avidity results indicate strong affinity to SUDV antigens. CONCLUSION: The detection of high level of seroreactivities against orthoebolaviruses in rural Cameroon where no outbreaks have been reported, raises the possibilities of silent circulation of orthoebolavirus, or of other not yet documented filoviruses, in these forested regions.

4.
J Infect Dis ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38487996

RESUMEN

The most recent Sudan virus (SUDV) outbreak in Uganda was first detected in September 2022 and resulted in 164 laboratory-confirmed cases and 77 deaths. There are no approved vaccines against SUDV. Here, we investigated the protective efficacy of ChAdOx1-biEBOV in cynomolgus macaques using a prime or a prime-boost regimen. ChAdOx1-biEBOV is a replication-deficient simian adenovirus vector encoding SUDV and Ebola virus (EBOV) glycoproteins (GPs). Intramuscular vaccination induced SUDV and EBOV GP-specific IgG responses and neutralizing antibodies. Upon challenge with SUDV, vaccinated animals showed signs of disease like those observed in control animals, and no difference in survival outcomes were measured among all three groups. Viral load in blood samples and in tissue samples obtained after necropsy were not significantly different between groups. Overall, this study highlights the importance of evaluating vaccines in multiple animal models and demonstrates the importance of understanding protective efficacy in both animal models and human hosts.

5.
BMC Genomics ; 25(1): 160, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38331741

RESUMEN

INTRODUCTION: The Ovar-DRB1 gene, a crucial element of the Major Histocompatibility Complex (MHC) Class II region, initiates adaptive immunity by presenting antigens to T-cells. Genetic diversity in sheep, particularly in MHC Class II genes like Ovar-DRB1, directly influences the specturm of presented antigens impacting immune responses and disease susceptability. Understanding the allelic diversity of Ovar-DRB1 gene in Sudan Desert Sheep (SDS) is essential for uncovering the genetic basis of immune responses and disease resistance, given the the breeds significance in Sudan's unique environment. METHODS: Utilizing Targeted Next-Generation Sequencing (NGS) we explore allelic diversity in Ovar-DRB1 gene within SDS. Successfully ampliying and and sequencing the second exon of this gene in 288 SDS samples representing six breeds provided a comprehensive allelic profile, enabling a detalied examination of the gene's genetic makeup. RESULTS: We identifed forty-six alleles, including four previously unreported, enrichness the genetic diversity of SDS breeds. These alleles exhibiting non-uniform distribution, varying frequencies across breeds, indicating a breed-specific genetic landscape. Certain alleles, known and novel, show higher frequencies in specific populations, suggesting potential associations with adaptive immune responses. Identifying these alleles sets the stage for investigating their functional roles and implications for disease resistance. Genetic differentiation among SDS breeds, as indicated by FST values and clustering analyses, highlights a unique genetic makeup shaped by geographic and historical factors. These differentiation patterns among SDS breeds have broader implications for breed conservation and targeted breeding to enhance disease resistance in specific populations. CONCLUSION: This study unveils Ovar-DRB1 gene allelic diversity in SDS breeds through targeted NGS and genetic analyses, revealing new alleles that underscore the breeds' unique genetic profile. Insights into the genetic factors governing immune responses and disease resistance emerge, promising for optimization of breeding strategies for enhanced livestock health in Sudan's unique environment.


Asunto(s)
Resistencia a la Enfermedad , Variación Genética , Ovinos/genética , Animales , Resistencia a la Enfermedad/genética , Sudán , Antígenos de Histocompatibilidad Clase II/genética , Alelos , Secuenciación de Nucleótidos de Alto Rendimiento
6.
J Virol ; 97(10): e0059023, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37750724

RESUMEN

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.


Asunto(s)
Brotes de Enfermedades , Ebolavirus , Variación Genética , Fiebre Hemorrágica Ebola , Humanos , Brotes de Enfermedades/estadística & datos numéricos , Ebolavirus/química , Ebolavirus/clasificación , Ebolavirus/genética , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/transmisión , Fiebre Hemorrágica Ebola/virología , Uganda/epidemiología , Trazado de Contacto
7.
Malar J ; 23(1): 200, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943203

RESUMEN

BACKGROUND: Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the staining technique and the technician's expertise. Therefore, there is a growing interest in next-generation, fully- or semi-integrated microscopes that can improve slide preparation and examination. This study aimed to evaluate the clinical performance of miLab™ (Noul Inc., Republic of Korea), a fully-integrated automated microscopy device for the detection of malaria parasites in symptomatic patients at point-of-care in Sudan. METHODS: This was a prospective, case-control diagnostic accuracy study conducted in primary health care facilities in rural Khartoum, Sudan in 2020. According to the outcomes of routine on-site microscopy testing, 100 malaria-positive and 90 malaria-negative patients who presented at the health facility and were 5 years of age or older were enrolled consecutively. All consenting patients underwent miLab™ testing and received a negative or suspected result. For the primary analysis, the suspected results were regarded as positive (automated mode). For the secondary analysis, the operator reviewed the suspected results and categorized them as either negative or positive (corrected mode). Nested polymerase chain reaction (PCR) was used as the reference standard, and expert light microscopy as the comparator. RESULTS: Out of the 190 patients, malaria diagnosis was confirmed by PCR in 112 and excluded in 78. The sensitivity of miLab™ was 91.1% (95% confidence interval [CI] 84.2-95.6%) and the specificity was 66.7% (95% Cl 55.1-67.7%) in the automated mode. The specificity increased to 96.2% (95% Cl 89.6-99.2%), with operator intervention in the corrected mode. Concordance of miLab with expert microscopy was substantial (kappa 0.65 [95% CI 0.54-0.76]) in the automated mode, but almost perfect (kappa 0.97 [95% CI 0.95-0.99]) in the corrected mode. A mean difference of 0.359 was found in the Bland-Altman analysis of the agreement between expert microscopy and miLab™ for quantifying parasite counts. CONCLUSION: When used in a clinical context, miLab™ demonstrated high sensitivity but low specificity. Expert intervention was shown to be required to improve the device's specificity in its current version. miLab™ in the corrected mode performed similar to expert microscopy. Before clinical application, more refinement is needed to ensure full workflow automation and eliminate human intervention. Trial registration ClinicalTrials.gov: NCT04558515.


Asunto(s)
Malaria , Microscopía , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Sudán , Microscopía/métodos , Humanos , Estudios de Casos y Controles , Estudios Prospectivos , Femenino , Masculino , Niño , Preescolar , Adulto , Adolescente , Malaria/diagnóstico , Adulto Joven , Persona de Mediana Edad
8.
Malar J ; 23(1): 170, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816778

RESUMEN

BACKGROUND: Nonadherence to national standards for malaria diagnosis and treatment has been reported in Sudan. In this study, qualitative research examined the clinical domains of nonadherence, factors influencing nonadherent practices and health workers' views on how to improve adherence. METHODS: In September 2023, five Focus Group Discussions (FGDs) were undertaken with 104 health workers from 42 health facilities in Sudan's Northern State. The participants included medical assistants, doctors, nurses, laboratory personnel, pharmacists and public health officers. The FGDs followed a semi-structured guide reflecting the national malaria case management protocol. Qualitative thematic analysis was performed. RESULTS: Nonadherent practices included disregarding parasitological test results, suboptimal paediatric artemether-lumefantrine (AL) dosing, lack of counselling, use of prohibited artemether injections for uncomplicated and severe malaria, artesunate dose approximations and suboptimal preparations, lack of AL follow on treatment for severe malaria; and rare use of primaquine for radical Plasmodium vivax treatment and dihydroartemisinin-piperaquine as the second-line treatment for uncomplicated malaria. Factors influencing nonadherence included stock-outs of anti-malarials and RDTs; staff shortages; lack of training, job aids and supervision; malpractice by specialists; distrust of malaria microscopy and RDTs; and patient pressure for diagnosis and treatment. Health workers recommended strengthening the supply chain; hiring personnel; providing in-service protocol training including specialists; establishing external quality assurance for malaria diagnosis; and providing onsite supportive supervision and public health campaigns. CONCLUSIONS: This study revealed a broad spectrum of behavioural and systemic challenges in malaria management among frontline health workers in Northern Sudan, including nonadherence to protocols due to resource shortages, training gaps, a lack of supportive supervision and patient pressure. These insights, including health workers' views about improvements, will inform evidence-based interventions by Sudan's National Malaria Control Programme to improve health systems readiness and the quality of malaria case management.


Asunto(s)
Antimaláricos , Manejo de Caso , Personal de Salud , Malaria , Sudán , Malaria/tratamiento farmacológico , Malaria/diagnóstico , Humanos , Antimaláricos/uso terapéutico , Investigación Cualitativa , Adhesión a Directriz/estadística & datos numéricos , Masculino , Grupos Focales , Femenino , Adulto
9.
Malar J ; 23(1): 33, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267985

RESUMEN

BACKGROUND: Seasonal malaria chemoprevention (SMC) is an effective intervention to prevent malaria in children in locations where the burden of malaria is high and transmission is seasonal. There is growing evidence suggesting that SMC with sulfadoxine-pyrimethamine and amodiaquine can retain its high level of effectiveness in East and Southern Africa despite resistance concerns. This study aims to generate evidence on the effectiveness of SMC when delivered under programmatic conditions in an area with an unknown anti-malarial drug resistance profile in the Northern Bahr el-Ghazal region of South Sudan. METHODS: A non-randomized quasi experimental study was conducted to compare an intervention county with a control county. Five monthly SMC cycles were delivered between July and November 2022, targeting about 19,000 children 3-59 months old. Data were obtained from repeated cross-sectional household surveys of caregivers of children aged 3-59 months using cluster sampling. Wave 1 survey took place in both counties before SMC implementation; Waves 2 and 3 took place after the second and fourth monthly SMC cycles. Difference-in-differences analyses were performed by fitting logistic regression models with interactions between county and wave. RESULTS: A total of 2760 children were sampled in the study across the three survey waves in both study counties. Children in the intervention arm had 70% lower odds of caregiver-reported fever relative to those in the control arm during the one-month period prior to Wave 2 (OR: 0.30, 95% CI 0.12-0.70, p = 0.003), and 37% lower odds in Wave 3 (OR: 0.63, 95% CI 0.22-1.59, p = 0.306) after controlling for baseline difference between counties in Wave 1. Odds of caregiver-reported RDT-confirmed malaria were 82% lower in the previous 1-month period prior to Wave 2 (OR: 0.18, 95% CI 0.07-0.49, p = 0.001) and Wave 3 (OR: 0.18, 95% CI 0.06-0.54, p = 0.003). CONCLUSION: These results show high effectiveness of SMC using SPAQ in terms of reducing malaria disease during the high transmission season in children 3-59 month. Despite the promising results, additional evidence and insights from chemoprevention efficacy cohort studies, and analyses of relevant resistance markers, are required to assess the suitability of SMC for this specific context.


Asunto(s)
Malaria , Niño , Humanos , Recién Nacido , Quimioprevención , Estudios Transversales , Malaria/prevención & control , Estaciones del Año , Sudán del Sur
10.
BMC Infect Dis ; 24(1): 543, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816800

RESUMEN

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.


Asunto(s)
Brotes de Enfermedades , Composición Familiar , Fiebre Hemorrágica Ebola , Humanos , Uganda/epidemiología , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/transmisión , Factores de Riesgo , Masculino , Adulto , Femenino , Estudios Retrospectivos , Estudios de Casos y Controles , Adolescente , Adulto Joven , Persona de Mediana Edad , Niño , Preescolar , Ebolavirus , Lactante
11.
BMC Infect Dis ; 24(1): 754, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080599

RESUMEN

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.


Asunto(s)
Brotes de Enfermedades , Humanos , Uganda/epidemiología , Femenino , Masculino , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/diagnóstico , Adulto , Sudán/epidemiología , Vigilancia de la Población/métodos , Fiebres Hemorrágicas Virales/epidemiología , Fiebres Hemorrágicas Virales/diagnóstico
12.
BMC Infect Dis ; 24(1): 520, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783244

RESUMEN

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.


Asunto(s)
Brotes de Enfermedades , Humanos , Uganda/epidemiología , Masculino , Estudios Transversales , Adulto , Femenino , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/virología , Secuenciación Completa del Genoma , Ebolavirus/genética , Ebolavirus/aislamiento & purificación
13.
BMC Infect Dis ; 24(1): 544, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816715

RESUMEN

INTRODUCTION: The COVID-19 pandemic is still a public health concern in South Sudan having caused suffering since the first case of COVID-19 was introduced on 28th February 2020. COVAX vaccines have since been introduced using a number of strategies including fixed site, temporary mobile, hit and run in flooded and conflict affected areas. We aim to describe the 2 ICVOPT campaigns that were conducted to improve the uptake and document lessons learnt during the initial rollout of the COVID-19 vaccination programin South Sudan between February 2022 and June 2022 each lasting for 7-days. METHODOLOGY: We conducted an operational cross-sectional descriptive epidemiological study of a series of the intensified COVID-19 vaccination Optimization (ICVOPT) campaigns from February 2022 to June 2022. Before the campaign, a bottom up micro-planning was conducted, validated by the County Health Departments (CHDs) and national MOH team. Each of the 2 campaigns lasted for 7 days targeting 30% of the eligible unvaccinated target population who were18 years and above. Each team consisted of 2 vaccinators, 2 recorders and 1 mobilizer. The teams employed both fixed site, temporary mobile, hit and run in flooded and conflict affected areas. The number of teams were calculated based on the daily workload per day (80 persons per team/day) for the duration of the campaigns. RESULTS: A total of 444,030 individuals were vaccinated with primary series COVID-19 vaccine (J&J) out of the targeted 635,030 persons. This represented 69.9% of target population in the selected 28 counties and 10 states of South Sudan in 7 days' ICVOPT campaigns. More eligible persons were reached in 7 days campaigns than the 9 months of rollout of the COVID-19 vaccine prior to ICVOPT campaigns using the fixed site strategy at the health facility posts. CONCLUSION: Intensified COVID-19 vaccination Optimization (ICVOPT) campaigns were vital and fast in scaling up vaccination coverages as compared to the fixed site vaccination strategies (2022 progress report on the Global Action Plan for Healthy Lives and Well-being for All Stronger collaboration for an equitable and resilient recovery towards the health-related Sustainable Development Goals, incentivizing collaboration, 2022) in complex humanitarian emergency settings and hard-to-reach areas of South Sudan.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Programas de Inmunización , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Sudán del Sur , Vacunas contra la COVID-19/administración & dosificación , Estudios Transversales , Programas de Inmunización/organización & administración , SARS-CoV-2/inmunología , Masculino , Adulto , Femenino , Adolescente , Vacunación
14.
J Fluoresc ; 34(1): 253-263, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37195542

RESUMEN

This study employed citric acid as a carbon source and thiourea as a sulphur source to conduct a straightforward one-step microwave synthesis of sulphur-doped carbon quantum dots (SCQDs). For the characterization of as-synthesized SCQDs, several methods such as fluorescence spectroscopy, X-Ray photoelectron spectroscopy (XPS), X-Ray diffraction (XRD), and zeta potential analyzer were utilized. XRD and XPS spectroscopy are used to examine the chemical composition and morphological aspects. These QDs have a limited size distribution spanning up to 5.89 nm, with a maximum distribution at 7 nm, according to zeta size analyser examinations. At an excitation wavelength of 340 nm, the highest fluorescence intensity (FL intensity) of SCQDs was attained. With a detection limit of 0.77 M, the synthesized SCQDs were employed as an efficient fluorescent probe for the detection of Sudan I in saffron samples.

15.
J Fluoresc ; 34(2): 635-653, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37338725

RESUMEN

We report the experimental and theoretical study of the diffraction patterns (DPs) and thermal properties of Sudan III. DPs are used in the calculation of the Sudan III nonlinear refractive index (NLRI), n 2 . As high as n 2 = 7.69 ×10-6 cm2/W is obtained. The study of the Sudan III thermal conductivity, TC, shows the reduction of the TC against the increase of the Sudan III temperature. The property, all-optical switching (AOS), is studied in details, both static and dynamic ones, using two, cw, visible, single mode laser beams of wavelengths 473 and 635 nm.

16.
BMC Vet Res ; 20(1): 296, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971746

RESUMEN

INTRODUCTION: Leptospirosis is a neglected emerging and zoonotic disease reported worldwide. This study sought to determine the molecular and serological prevalence of Leptospira spp. and the associated risk factors in slaughtered cattle from the Bahr El Ghazal region of South Sudan. MATERIALS AND METHODS: Between January 16th and February 25th, 2023, blood and urine samples were collected from 402 cattle at the Lokoloko Municipal Slaughterhouse in Western Bahr El-Ghazal State. Serum samples were tested using the microscopic agglutination test (MAT), with a panel of 12 serovars (sv) from 12 serogroups (sg) and 4 species (spp) of Leptospira spp. These serovars had been previously identified in Sudan and the East African region. Simultaneously, 400 corresponding urine samples were screened using qualitative real-time polymerase chain reaction (PCR) to detect the shedding of Leptospira spp. in urine. To identify the associated risk factors, the age, sex, breed and body condition score of each sampled cattle was noted at the time of sampling and subsequently analysed using logistic regression models. RESULTS: Among the 402 serum samples screened, a substantial 81.8% (329/402, 95% CI 77.9-85.3) displayed seropositivity for Leptospira spp. with a MAT titre ≥ 100. The prevalence of urine shedding determined by PCR was 6% (23/400, 95% CI 3.8-8.4), while probable recent leptospirosis with a MAT ≥ 1:800 was observed in 33.1% (133/402, 95% CI 28.6-37.8) of the cattle. Multiple reactions were detected in 34.8% (140/402, 95% CI 30.6-39.5) serum samples. The seropositivity was against L. borgpetersenii sg. Tarassovi (78.6%; 316/402, 95% CI 74.4-82.3), followed by L. borgpetersenii sg. Ballum at 20.4% (82/402, 95% CI, 16.7-24.4%), L. kirschneri sg. Autumnalis At 8.7% (35/402, 95% CI 5.7-11.7), L. interrogans sg. of Pomona at 7.0% (28/402, 95% CI 4.5-9.5), and L. interrogans sg. Hebdomadis was 5.0% (20/402, 95% CI 2.8-7.2). Several risk factors are associated with seropositivity. Older animals (≥ 2 years) had 2.0 times greater odds (95% CI 1.14-3.5) of being seropositive than younger animals (< 2 years), P-value = 0.016. Female animals demonstrated 2.1 times greater odds (95% CI 1.2-3.6) of seropositivity than males did (P-value = 0.008). Additionally, Felata/Mbororo cattle exhibited 2.4 times greater odds (95% CI 1.3-4.5) of being seropositive than did local Nilotic cattle (P-value = 0.005). The agreement between the MAT and PCR results was poor, as indicated by a kappa statistic value of 0.001 and a P-value of 0.913. But there was a moderate agreement between MAT high titres ≥ 800 and PCR positivity with a kappa statistic value = 0.501 and a P-value < 0.001. CONCLUSION: In addition to the high seroprevalence, Leptospira spp. were found in the urine of slaughtered cattle, suggesting that leptospirosis is endemic to the study area. This finding underscores the significance of cattle as potential sources of infection for slaughterhouse workers, the general public, and other animal species. To address this issue effectively in the Bahr El Ghazal Region and South Sudan, a comprehensive strategy involving a multidisciplinary approach is essential to minimize disease among animals, hence reducing potential zoonotic risks to humans.


Asunto(s)
Mataderos , Enfermedades de los Bovinos , Leptospira , Leptospirosis , Animales , Bovinos , Leptospirosis/veterinaria , Leptospirosis/epidemiología , Leptospirosis/microbiología , Leptospira/aislamiento & purificación , Leptospira/genética , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Factores de Riesgo , Femenino , Masculino , Prevalencia , Sudán del Sur/epidemiología , Estudios Seroepidemiológicos , Anticuerpos Antibacterianos/sangre
17.
BMC Pregnancy Childbirth ; 24(1): 225, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561681

RESUMEN

BACKGROUND: Globally, mistreatment of women during labor and delivery is a common human rights violation. Person-centered maternity care (PCMC), a critical component of quality of care, is respectful and responsive to an individual's needs and preferences. Factors related to poor PCMC are often exacerbated in humanitarian settings. METHODS: We conducted a qualitative study to understand Sudanese refugee women's experiences, including their perceptions of quality of care, during labor and delivery at the maternities in two refugee camps in eastern Chad, as well as maternity health workers' perceptions of PCMC and how they could be better supported to provide this. In-depth interviews were conducted individually with 22 women who delivered in the camp maternities and five trained midwives working in the two maternities; and in six dyads with a total of 11 Sudanese refugee traditional birth attendants and one assistant midwife. In addition, facility assessments were conducted at each maternity to determine their capacity to provide PCMC. RESULTS: Overall, women reported positive experiences in the camp maternities during labor and delivery. Providers overwhelmingly defined respectful care as patient-centered and respect as being something fundamental to their role as health workers. While very few reported incidents of disrespect between providers and patients in the maternity, resource constraints, including overwork of the providers and overcrowding, resulted in some women feeling neglected. CONCLUSIONS: Despite providers' commitment to offering person-centered care and women's generally positive experiences in this study, one of few that explored PCMC in a refugee camp, conflict and displacement exacerbates the conditions that contribute to mistreatment during labor and delivery. Good PCMC requires organizational emphasis and support, including adequate working conditions and ensuring suitable resources so health workers can effectively perform.


Asunto(s)
Servicios de Salud Materna , Refugiados , Femenino , Humanos , Embarazo , Campos de Refugiados , Chad , Actitud del Personal de Salud , Investigación Cualitativa , Atención Dirigida al Paciente , Parto , Calidad de la Atención de Salud , Parto Obstétrico
18.
BMC Nephrol ; 25(1): 171, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769490

RESUMEN

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.


Asunto(s)
Fenofibrato , Losartán , Rigidez Vascular , Humanos , Masculino , Adulto , Losartán/uso terapéutico , Rigidez Vascular/efectos de los fármacos , Fenofibrato/uso terapéutico , Quimioterapia Combinada , Hipolipemiantes/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Apolipoproteínas E/genética
19.
BMC Public Health ; 24(1): 235, 2024 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243167

RESUMEN

BACKGROUND: During 2020 and immediately prior to the COVID-19 pandemic, Sudan was experiencing multiple emergencies including violence, seasonal flooding, and vector-borne disease outbreaks. After more than ten years since its last case of wild poliovirus, Sudan declared a circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreak on 9 August 2020. METHODS: cVDPV2 outbreak response data and programme documents of the Federal Ministry of Health and WHO were reviewed. Surveillance data was verified through WHO-recommended procedures for detecting and characterizing polioviruses from stool and sewage samples collected from acute flaccid paralysis (AFP) cases and the environment. RESULTS: This outbreak in Sudan led to a total of 58 confirmed cases of cVDPV2 from 15 of the 18 states. Two nationwide vaccination campaigns were held to increase immunity of children under-five against poliovirus type 2. Funding challenges were overcome by intense additional resource mobilization from in-country sources. The funding gap was bridged from domestic resources (49%) sourced through GPEI partners, and in-country humanitarian funding mechanisms. CONCLUSIONS: During an outbreak response and challenge of funding shortfall, mobilizing in-country resources is possible through coordinated approaches, regular communication with partners, disaggregation of needs, and matching in-kind and financial support to fill gaps. A cVDPV2 outbreak requires a fast, resourced, and quality response to stop virus circulation.


Asunto(s)
Poliomielitis , Poliovirus , Humanos , Brotes de Enfermedades , Urgencias Médicas , Pandemias , Poliomielitis/epidemiología , Poliomielitis/prevención & control , Vacuna Antipolio Oral , Sudán/epidemiología , Lactante , Preescolar
20.
BMC Public Health ; 24(1): 895, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532360

RESUMEN

INTRODUCTION: With low COVID-19 vaccination coverage, non-pharmaceutical interventions were critical to mitigating the COVID-19 pandemic in Sudan. We explored changes in social contact patterns, risk perception, attitudes, and practices toward protective measures during an evolving COVID-19 outbreak in six illustrative communities in Sudan. METHODS: This qualitative study took place in six communities in five Sudanese states using focus group discussions with community members and non-participant structured observations in public spaces between March 2021 and April 2021. A total of 117 participants joined 24 group discussions. We used a two-stage thematic analysis. RESULTS: The perceived importance of compliance with individual preventative measures among those who believe in COVID-19 was higher than observed compliance with behaviors in most study sites. Adherence was consistently low and mainly driven by enforced movement restrictions. As restrictions were lifted, social contacts outside the household resumed pre-COVID-19 levels, and risk perception and individual and institutional adherence to protective measures diminished. We identified an environment that is socially and economically unsupportive of preventive practices, compounded by widespread rumours, misinformation, and mistrust in the government-led response. However, we identified new social habits that can contribute to reducing COVID-19 transmission. CONCLUSION: The unfavourable social and economic environment, coupled with the low visibility of the pandemic and pandemic response, has likely modulated the influence of higher risk perception on adopting precautionary behaviours by individuals. Governments and non-governmental actors should increase the visibility of the pandemic and pandemic response, enforce and incentivise infection control measures in public areas, promote emerging preventive social habits, and actively track and address rumours and misinformation related to COVID-19 and COVID-19 vaccines.


Asunto(s)
COVID-19 , Humanos , Vacunas contra la COVID-19 , Pandemias/prevención & control , Sudán , Actitud
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