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1.
J Infect Dis ; 228(Suppl 7): S721-S729, 2023 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-37474155

RESUMEN

Vesicular stomatitis virus-Ebola virus (VSV-EBOV) vaccine has been successfully used in ring vaccination approaches during EBOV disease outbreaks demonstrating its general benefit in short-term prophylactic vaccination, but actual proof of its benefit in true postexposure prophylaxis (PEP) for humans is missing. Animal studies have indicated PEP efficacy when VSV-EBOV was used within hours of lethal EBOV challenge. Here, we used a lower EBOV challenge dose and a combined intravenous and intramuscular VSV-EBOV administration to improve PEP efficacy in the rhesus macaque model. VSV-EBOV treatment 1 hour after EBOV challenge resulted in delayed disease progression but little benefit in outcome. Thus, we could not confirm previous results indicating questionable benefit of VSV-EBOV for EBOV PEP in a nonhuman primate model.


Asunto(s)
Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Humanos , Animales , Macaca mulatta , Vesiculovirus , Virus de la Estomatitis Vesicular Indiana
2.
J Infect Dis ; 228(Suppl 7): S474-S478, 2023 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-37596837

RESUMEN

Although there are now approved treatments and vaccines for Ebola virus disease, the case fatality rate remains unacceptably high even when patients are treated with the newly approved therapeutics. Furthermore, these countermeasures are not expected to be effective against disease caused by other filoviruses. A meeting of subject-matter experts was held during the 10th International Filovirus Symposium to discuss strategies to address these gaps. Several investigational therapeutics, vaccine candidates, and combination strategies were presented. The greatest challenge was identified to be the implementation of well-designed clinical trials of safety and efficacy during filovirus disease outbreaks. Preparing for this will require agreed-upon common protocols for trials intended to bridge multiple outbreaks across all at-risk countries. A multinational research consortium including at-risk countries would be an ideal mechanism to negotiate agreement on protocol design and coordinate preparation. Discussion participants recommended a follow-up meeting be held in Africa to establish such a consortium.


Asunto(s)
Ebolavirus , Infecciones por Filoviridae , Filoviridae , Fiebre Hemorrágica Ebola , Humanos , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/epidemiología , Brotes de Enfermedades/prevención & control , África
3.
MMWR Morb Mortal Wkly Rep ; 71(8): 290-292, 2022 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-35202354

RESUMEN

On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff members at biosafety level 4 facilities in the United States (1).


Asunto(s)
Vacunas contra el Virus del Ébola/administración & dosificación , Fiebre Hemorrágica Ebola/prevención & control , Exposición Profesional/prevención & control , Vacunación , Adulto , Comités Consultivos , Centers for Disease Control and Prevention, U.S. , Personal de Salud , Directrices para la Planificación en Salud , Humanos , Personal de Laboratorio , Estados Unidos/epidemiología
5.
BMC Infect Dis ; 20(1): 117, 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32041536

RESUMEN

BACKGROUND: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens. METHOD: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated. RESULTS: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella, Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients. CONCLUSION: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.


Asunto(s)
Pruebas Diagnósticas de Rutina/normas , Fiebre/diagnóstico , África/epidemiología , Asia/epidemiología , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/parasitología , Infecciones Comunitarias Adquiridas/virología , Países en Desarrollo , Fiebre/microbiología , Fiebre/parasitología , Fiebre/virología , Salud Global/normas , Humanos , América Latina/epidemiología , Prevalencia
7.
N Engl J Med ; 372(1): 40-7, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25372658

RESUMEN

BACKGROUND: In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. METHODS: From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. RESULTS: Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). CONCLUSIONS: Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.


Asunto(s)
Deshidratación/etiología , Fiebre Hemorrágica Ebola/complicaciones , Fiebre Hemorrágica Ebola/mortalidad , Adulto , Factores de Edad , Antiinfecciosos/uso terapéutico , Diarrea/etiología , Ebolavirus , Epidemias , Femenino , Fiebre/etiología , Fluidoterapia , Guinea/epidemiología , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Riesgo , Tasa de Supervivencia , Taquicardia/etiología , Vómitos/etiología
8.
Curr Top Microbiol Immunol ; 411: 93-113, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28646340

RESUMEN

The low-resource environment deprives healthcare providers caring for patients with Ebola virus disease (EVD) of many of the means employed for the critically ill that are available in better resourced settings, such as advanced therapeutic interventions and abundant staff. In addition to these limitations may be added those imposed by the remote tropical locations, where EVD outbreaks occur. In this setting, a safe environment is created where healthcare workers may care for their patients over the evolving course of their acute illness into their convalescent period. Clinical management of EVD combines supportive and symptomatic care while also addressing the patient's emotional and mental health needs. A variety of specific therapies directly targeting the virus has become available, but none of these has, as of yet, conclusively demonstrated an impact. Healthcare workers caring for EVD patients must be constantly aware that they are part of a larger epidemic control operation, and their actions have consequences that go beyond their patients to their families and the community affected by the outbreak.


Asunto(s)
Recursos en Salud/provisión & distribución , Fiebre Hemorrágica Ebola/terapia , Brotes de Enfermedades , Personal de Salud/estadística & datos numéricos , Recursos en Salud/economía , Fiebre Hemorrágica Ebola/economía , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/virología , Humanos
9.
J Infect Dis ; 215(2): 171-174, 2017 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-28073857

RESUMEN

A neonate born to an Ebola virus-positive woman was diagnosed with Ebola virus infection on her first day of life. The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734. On day 20, a venous blood specimen tested negative for Ebola virus by quantitative reverse-transcription polymerase chain reaction. The patient was discharged in good health on day 33 of life. Further follow-up consultations showed age-appropriate weight gain and neurodevelopment at the age of 12 months. This patient is the first neonate documented to have survived congenital infection with Ebola virus.


Asunto(s)
Alanina/análogos & derivados , Anticuerpos Monoclonales/administración & dosificación , Antivirales/administración & dosificación , Fiebre Hemorrágica Ebola/congénito , Fiebre Hemorrágica Ebola/terapia , Factores Inmunológicos/administración & dosificación , Ribonucleótidos/administración & dosificación , Terapias en Investigación/métodos , Adenosina Monofosfato/análogos & derivados , Alanina/administración & dosificación , Sangre/virología , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Tratamiento , Adulto Joven
10.
J Infect Dis ; 214(suppl 3): S294-S296, 2016 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-27707893

RESUMEN

Cases of relapsed Ebola virus disease involving symptoms in the central nervous system are reminiscent of our past observations with some nonhuman primates (NHPs) that survived acute Ebola virus infection. We document our findings in detail here and suggest that this phenomenon can be further investigated in NHPs.


Asunto(s)
Sistema Nervioso Central/virología , Ebolavirus/patogenicidad , Fiebre Hemorrágica Ebola/virología , Animales , Humanos , Recurrencia
11.
J Infect Dis ; 214(suppl 3): S145-S152, 2016 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-27365495

RESUMEN

BACKGROUND: Ebola viruses (EBOVs) are primarily transmitted by contact with infected body fluids. Ebola treatment centers (ETCs) contain areas that are exposed to body fluids through the care of patients suspected or confirmed to have EBOV disease. There are limited data documenting which areas/fomites within ETCs pose a risk for potential transmission. This study conducted environmental surveillance in 2 ETCs in Freetown, Sierra Leone, during the 2014-2016 West African Ebola outbreak. METHODS: ETCs were surveyed over a 3-week period. Sites to be swabbed were identified with input from field personnel. Swab samples were collected and tested for the presence of EBOV RNA. Ebola-positive body fluid-impregnated cotton pads were serially sampled. RESULTS: General areas of both ETCs were negative for EBOV RNA. The immediate vicinity of patients was the area most likely to be positive for EBOV RNA. Personal protective equipment became positive during patient care, but chlorine solution washes rendered them negative. CONCLUSIONS: Personal protective equipment and patient environs do become positive for EBOV RNA, but careful attention to decontamination seems to remove it. EBOV RNA was not detected in general ward spaces. Careful attention to decontamination protocols seems to be important in minimizing the presence of EBOV RNA within ETC wards.


Asunto(s)
Brotes de Enfermedades , Ebolavirus/aislamiento & purificación , Microbiología Ambiental , Fómites/virología , Fiebre Hemorrágica Ebola/epidemiología , Líquidos Corporales/virología , Ebolavirus/genética , Personal de Salud , Fiebre Hemorrágica Ebola/virología , Hospitales , Humanos , ARN Viral/análisis , Riesgo , Sierra Leona/epidemiología
12.
J Infect Dis ; 214(suppl 3): S303-S307, 2016 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-27471319

RESUMEN

The development of point-of-care clinical chemistry analyzers has enabled the implementation of these ancillary tests in field laboratories in resource-limited outbreak areas. The Eternal Love Winning Africa (ELWA) outbreak diagnostic laboratory, established in Monrovia, Liberia, to provide Ebola virus and Plasmodium spp. diagnostics during the Ebola epidemic, implemented clinical chemistry analyzers in December 2014. Clinical chemistry testing was performed for 68 patients in triage, including 12 patients infected with Ebola virus and 18 infected with Plasmodium spp. The main distinguishing feature in clinical chemistry of Ebola virus-infected patients was the elevation in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase levels and the decrease in calcium. The implementation of clinical chemistry is probably most helpful when the medical supportive care implemented at the Ebola treatment unit allows for correction of biochemistry derangements and on-site clinical chemistry analyzers can be used to monitor electrolyte balance.


Asunto(s)
Brotes de Enfermedades , Epidemias , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/epidemiología , Malaria/diagnóstico , Adolescente , Alanina Transaminasa/análisis , Fosfatasa Alcalina/análisis , Aspartato Aminotransferasas/análisis , Química Clínica , Servicios de Laboratorio Clínico , Ebolavirus/inmunología , Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/virología , Humanos , Liberia/epidemiología , Pruebas de Función Hepática , Malaria/epidemiología , Malaria/parasitología , Masculino , Plasmodium/aislamiento & purificación , Plasmodium/metabolismo , Sistemas de Atención de Punto , gamma-Glutamiltransferasa/análisis
13.
Clin Infect Dis ; 63(8): 1026-33, 2016 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-27531847

RESUMEN

BACKGROUND: The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. METHODS: All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. RESULTS: The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. CONCLUSIONS: Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.


Asunto(s)
Coinfección , Ebolavirus , Fiebre Hemorrágica Ebola/complicaciones , Fiebre Hemorrágica Ebola/mortalidad , Malaria/complicaciones , Malaria/parasitología , Parasitemia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Modelos Animales de Enfermedad , Ebolavirus/genética , Femenino , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Lactante , Recién Nacido , Malaria/diagnóstico , Malaria/epidemiología , Masculino , Ratones , Persona de Mediana Edad , Carga de Parásitos , Plasmodium/genética , Tasa de Supervivencia , Carga Viral , Adulto Joven
14.
Emerg Infect Dis ; 22(2): 210-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26812466

RESUMEN

Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.


Asunto(s)
Ebolavirus/genética , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/virología , Tipificación Molecular/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Genes Virales , Guinea , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Tipificación Molecular/normas , ARN Viral , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
15.
Emerg Infect Dis ; 22(2): 323-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26814608

RESUMEN

Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection.


Asunto(s)
Coinfección , Brotes de Enfermedades , Ebolavirus , Fiebre Hemorrágica Ebola/epidemiología , Malaria/diagnóstico , Malaria/parasitología , Humanos , Malaria Falciparum/diagnóstico , Malaria Falciparum/parasitología , Carga de Parásitos , Plasmodium falciparum/clasificación , Plasmodium falciparum/genética , Prevalencia
17.
J Infect Dis ; 212 Suppl 2: S98-S100, 2015 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25821225

RESUMEN

Personal protective equipment (PPE) is an important part of worker protection during filovirus outbreaks. The need to protect against a highly virulent fluid-borne pathogen in the tropical environment imposes a heat stress on the wearer that is itself a safety risk. No evidence supports the choice of PPE employed in recent outbreaks, and standard testing procedures employed by the protective garment industry do not well simulate filovirus exposure. Further research is needed to determine the appropriate PPE for filoviruses and the heat stress that it imposes.


Asunto(s)
Infecciones por Filoviridae/epidemiología , Infecciones por Filoviridae/prevención & control , Filoviridae/patogenicidad , Equipo de Protección Personal/virología , Brotes de Enfermedades , Epidemias , Infecciones por Filoviridae/virología , Humanos
18.
N Engl J Med ; 377(15): 1480-1482, 2017 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-26465064
20.
Glob Health Action ; 17(1): 2331291, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38666727

RESUMEN

BACKGROUND: There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high. OBJECTIVES: The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak. METHODS: We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design. RESULTS: Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area. CONCLUSION: Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.


Main findings: For humanitarian organizations it is imperative to document the methodological limitations of cluster surveys and discuss the utility.Added knowledge: This paper adds new knowledge on cluster surveys for highly clustered data such us in Ebola virus disease.Global health impact of policy and action: We provided empirical estimates and discuss design improvements to inform future study.


Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Humanos , Sierra Leona/epidemiología , Fiebre Hemorrágica Ebola/mortalidad , Fiebre Hemorrágica Ebola/epidemiología , Estudios Retrospectivos , Adulto , Femenino , Adolescente , Preescolar , Masculino , Persona de Mediana Edad , Adulto Joven , Análisis por Conglomerados , Niño , Lactante , Población Rural/estadística & datos numéricos , Población Urbana , Encuestas y Cuestionarios
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