Long-term #immunity against #yellowfever in #children vaccinated during infancy: a longitudinal cohort study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal cohort study

Cristina Domingo, Juliane Fraissinet, Patrick O Ansah, Corey Kelly, Niranjan Bhat, Samba O Sow, José E Mejía

Open Access / Published: September 19, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30323-8




A single dose of vaccine against yellow fever is routinely administered to infants aged 9–12 months under the Expanded Programme on Immunization, but the long-term outcome of vaccination in this age group is unknown. We aimed to evaluate the long-term persistence of neutralising antibodies to yellow fever virus following routine vaccination in infancy.


We did a longitudinal cohort study, using a microneutralisation assay to measure protective antibodies against yellow fever in Malian and Ghanaian children vaccinated around age 9 months and followed up for 4·5 years (Mali), or 2·3 and 6·0 years (Ghana). Healthy children with available day-0 sera, a complete follow-up history, and no record of yellow fever revaccination were included; children seropositive for yellow fever at baseline were excluded. We standardised antibody concentrations with reference to the yellow fever WHO International Standard.


We included 587 Malian and 436 Ghanaian children vaccinated between June 5, 2009, and Dec 26, 2012. In the Malian group, 296 (50·4%, 95% CI 46·4–54·5) were seropositive (antibody concentration ≥0·5 IU/mL) 4·5 years after vaccination. Among the Ghanaian children, 121 (27·8%, 23·5–32·0) were seropositive after 2·3 years. These results show a large decrease from the proportions of seropositive infants 28 days after vaccination, 96·7% in Mali and 72·7% in Ghana, reported by a previous study of both study populations. The number of seropositive children increased to 188 (43·1%, 95% CI 38·5–47·8) in the Ghanaian group 6·0 years after vaccination, but this result might be confounded by unrecorded revaccination or natural infection with wild yellow fever virus during a 2011–12 outbreak in northern Ghana.


Rapid waning of immunity during the early years after vaccination of 9-month-old infants argues for a revision of the single-dose recommendation for this target population in endemic countries. The short duration of immunity in many vaccinees suggests that booster vaccination is necessary to meet the 80% population immunity threshold for prevention of yellow fever outbreaks.


Wellcome Trust.

Keywords: Yellow Fever; Vaccines; Pediatrics.



Previous #dengue or #Zika virus #exposure can drive to #infection #enhancement or neutralisation of other #flaviviruses (Mem Inst Oswaldo Cruz, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Mem Inst Oswaldo Cruz. 2019;114:e190098. doi: 10.1590/0074-02760190098. Epub 2019 Aug 12.

Previous dengue or Zika virus exposure can drive to infection enhancement or neutralisation of other flaviviruses.

Oliveira RA1,2, de Oliveira-Filho EF1,3, Fernandes AI4,5, Brito CA6, Marques ET1,7, Tenório MC1, Gil LH1.

Author information: 1 Fundação Oswaldo Cruz, Instituto Aggeu Magalhães, Departamento de Virologia, Recife, PE, Brasil. 2 Universidade Federal da Paraíba, Departamento de Fisiologia e Patologia, João Pessoa, PB, Brasil. 3 Charité-Universitätsmedizin Berlin, Berlin, Germany. 4 Universidade Federal da Paraíba, Hospital Universitário Lauro Wanderley, Serviço de Doenças Infecciosas e Parasitárias, João Pessoa, PB, Brasil. 5 Universidade Federal da Paraíba, Escola Técnica de Saúde, Grupo de Estudos e Pesquisas em Imunologia Humana, João Pessoa, PB, Brasil. 6 Universidade Federal de Pernambuco, Departamento de Medicina Clínica, Recife, PE, Brasil. 7 University of Pittsburgh, Center for Vaccine Research, Department of Infectious Diseases and Microbiology, Pittsburgh, PA, USA.




Dengue virus (DENV) has circulated in Brazil for over 30 years. During this time, one serotype has cyclically replaced the other, until recently, when all four distinct serotypes began to circulate together. Persistent circulation of DENV for long time periods makes sequential infections throughout a person’s life possible. After primary DENV infection, life-long immunity is developed for the infecting serotype. Since DENV and Zika virus (ZIKV) are antigenically similar, the possibility of cross-reactions has attracted attention and has been demonstrated in vitro.


The aim of this study was to investigate whether immune-sera from DENV and ZIKV infected patients would cross-react in vitro with other Flaviviridae family members.


Cross-reaction of the studied samples with yellow fever virus (YFV), West Nile virus (WNV), Rocio virus (ROCV), Saint Louis virus (SLEV) and Ilheus virus (ILHV) has been investigated by plaque reduction neutralisation test (PRNT) and the antibody-dependent enhancement (ADE) by flow-cytometry.


Antibodies against ZIKV and DENV virus cross-reacted with other flaviviruses either neutralising or enhancing the infection. Thus, viral entrance into FcRFcɣRII-expressing cells were influenced by the cross-reactive antibodies. ZIKV or DENV immune sera enhanced cellular infection by WNV, ILHV, ROCV and SLEV. Finally, DENV immune sera presented higher neutralising activity for YFV and SLEV. While ZIKV immune sera neutralised WNV, ILHV and ROCV with high frequencies of positivity.


The co-circulation of those viruses in the same area represents a risk for the development of severe infections if they spread throughout the country. Successive flavivirus infections may have an impact on disease pathogenesis, as well as on the development of safe vaccine strategies.

PMID: 31411310 DOI: 10.1590/0074-02760190098

Keywords: Flavivirus; Dengue fever; Zika Virus; WNV; Rocio Virus; St Louis Virus; Ilheus virus; Yellow Fever; Serology; ADE; Brazil.


#Immunogenicity of #Fractional-Dose #Vaccine during a #YellowFever #Outbreak — Final #Report (N Engl J Med., abstract)

[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]

Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak — Final Report

Rebecca M. Casey, M.B., B.S., M.P.H., Jennifer B. Harris, Ph.D., M.P.H., Steve Ahuka-Mundeke, M.D., Ph.D., Meredith G. Dixon, M.D., Gabriel M. Kizito, M.D., Pierre M. Nsele, M.D., Grace Umutesi, M.P.H., Janeen Laven, B.S., Olga Kosoy, M.S., Gilson Paluku, M.D., M.P.H., Abdou S. Gueye, M.D., Ph.D., Terri B. Hyde, M.D., M.P.H., et al.




In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign.


We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response.


Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons).


A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.)

Keywords: Yellow Fever; Vaccines; Angola; DRC.


#Ultrasound-guided minimally invasive #autopsy as a tool for rapid post-mortem #diagnosis in the 2018 Sao Paulo #yellowfever #epidemic: Correlation with conventional autopsy (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Ultrasound-guided minimally invasive autopsy as a tool for rapid post-mortem diagnosis in the 2018 Sao Paulo yellow fever epidemic: Correlation with conventional autopsy

Amaro Nunes Duarte-Neto, Renata Aparecida de Almeida Monteiro, Janaina Johnsson, Marielton dos Passos Cunha, Shahab Zaki Pour, Amanda Cartagenes Saraiva, Yeh-Li Ho, Luiz Fernando Ferraz da Silva, Thais Mauad, Paolo Marinho de Andrade Zanotto, Paulo Hilário Nascimento Saldiva, Ilka Regina Souza de Oliveira, Marisa Dolhnikoff

Published: July 22, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007625 / This is an uncorrected proof.




New strategies for collecting post-mortem tissue are necessary, particularly in areas with emerging infections. Minimally invasive autopsy (MIA) has been proposed as an alternative to conventional autopsy (CA), with promising results. Previous studies using MIA addressed the cause of death in adults and children in developing countries. However, none of these studies was conducted in areas with an undergoing infectious disease epidemic. We have recently experienced an epidemic of yellow fever (YF) in Brazil. Aiming to provide new information on low-cost post-mortem techniques that could be applied in regions at risk for infectious outbreaks, we tested the efficacy of ultrasound-guided MIA (MIA-US) in the diagnosis of patients who died during the epidemic.

Methodology/principal findings

In this observational study, we performed MIA-US in 20 patients with suspected or confirmed YF and compared the results with those obtained in subsequent CAs. Ultrasound-guided biopsies were used for tissue sampling of liver, kidneys, lungs, spleen, and heart. Liver samples from MIA-US and CA were submitted for RT-PCR and immunohistochemistry for detection of YF virus antigen. Of the 20 patients, 17 had YF diagnosis confirmed after autopsy by histopathological and molecular analysis. There was 100% agreement between MIA-US and CA in determining the cause of death (panlobular hepatitis with hepatic failure) and main disease (yellow fever). Further, MIA-US obtained samples with good quality for molecular studies and for the assessment of the systemic involvement of the disease. Main extrahepatic findings were pulmonary hemorrhage, pneumonia, acute tubular necrosis, and glomerulonephritis. One patient was a 24-year-old, 27-week pregnant woman; MIA-US assessed the placenta and provided adequate placental tissue for analysis.


MIA-US is a reliable tool for rapid post-mortem diagnosis of yellow fever and can be used as an alternative to conventional autopsy in regions at risk for hemorrhagic fever outbreaks with limited resources to perform complete diagnostic autopsy.


Author summary

Reliable mortality information is of paramount importance to establish sound public health policies. Autopsy is an important tool not only for determining the cause of death, but also for the detection of novel diseases. In the last decades, we have been globally identifying an unprecedented number of emerging infections. Therefore, there is great interest in the development of less invasive and low-cost tools for the accurate post-mortem diagnosis in fatal cases. Minimally invasive autopsy (MIA), conceived as targeting diagnostic biopsies of key organs by needle puncture, has been proposed as an alternative to conventional autopsy (CA) for the determination of cause of death in developing countries. In this research, we tested the efficacy of MIA in the post-mortem diagnosis of 20 patients with suspected or confirmed yellow fever who died during the recent epidemic of yellow fever that occurred in Brazil. There was a perfect agreement between MIA and CA in determining the cause of death (hepatic failure) and main disease (yellow fever) in all patients with confirmed yellow fever. This finding indicates that MIA can be used as an alternative to CA in regions at risk for infectious disease outbreaks with limited resources to perform conventional autopsies.


Citation: Duarte-Neto AN, Monteiro RAdA, Johnsson J, Cunha MdP, Pour SZ, Saraiva AC, et al. (2019) Ultrasound-guided minimally invasive autopsy as a tool for rapid post-mortem diagnosis in the 2018 Sao Paulo yellow fever epidemic: Correlation with conventional autopsy. PLoS Negl Trop Dis 13(7): e0007625. https://doi.org/10.1371/journal.pntd.0007625

Editor: Christine A. Petersen, University of Iowa, UNITED STATES

Received: February 8, 2019; Accepted: July 10, 2019; Published: July 22, 2019

Copyright: © 2019 Duarte-Neto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: This work was funded by the Bill & Melinda Gates Foundation (https://www.gatesfoundation.org/), Fundação de Amparo à Pesquisa do Estado de São Paulo (http://www.fapesp.br/). PMdAZ was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (http://www.cnpq.br/), process # 441105/2016-5. MdPC received a scholarship from Fundação de Amparo à Pesquisa do Estado de São Paulo, process # 2016/08204-2. MD, PHNS, and TM receive individual grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Yellow fever; Anatomo-patology; Brazil.


#Nucleoside Analogs with #Antiviral Activity Against #YellowFever Virus (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents ahd Chemotherapy, full page: (LINK). Abstract, edited.]

Nucleoside Analogs with Antiviral Activity Against Yellow Fever Virus

Keivan Zandi, Franck Amblard, Sarah Amichai, Leda Bassit, Sijia Tao, Yong Jiang, Longhu Zhou, Olivia Ollinger Russell, Seema Mengshetti, Raymond F. Schinazi

DOI: 10.1128/AAC.00889-19



Yellow fever virus (YFV) is a human flavivirus re-emerging in parts of the world. While a vaccine is available, large outbreaks have recently occurred in Brazil and certain African countries. Development of effective antiviral against YFV is crucial as there is no available effective drug against YFV. We have identified several novel nucleoside analogs with potent antiviral activity against YFV with EC50 values between 0.25 to 1 μM with selectivity indices over 100 in culture.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Yellow fever.


Boosting #Global #YellowFever #Vaccine #Supply for #Epidemic #Preparedness: 3 Actions for #China and the #USA (Virol Sin., abstract)

[Source: Virologica Sinica, full page: (LINK). Summary, edited.]

Boosting Global Yellow Fever Vaccine Supply for Epidemic Preparedness: 3 Actions for China and the USA

Authors: Daniel R. Lucey, Kristen R. Kent

Perspective / First Online: 24 May 2019


Yellow fever (YF) is an acute disease caused by a flavivirus that infects the liver. It can cause jaundice, bleeding, kidney damage, and death. No antiviral therapy exists. A vaccine does exist, however, and fortunately confers life-long immunity after a single dose (Monath et al.2016; WHO 2017a, b).




Compliance with Ethical Standards

Conflict of interest: The authors declare that they have no conflict of interest.

Animal and Human Rights Statement: This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: Yellow Fever; Vaccines; USA; China.


#Serological #evidence of #Flavivirus #circulation in #human populations in Northern #Kenya: an assessment of disease risk 2016-2017 (Virol J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virol J. 2019 May 17;16(1):65. doi: 10.1186/s12985-019-1176-y.

Serological evidence of Flavivirus circulation in human populations in Northern Kenya: an assessment of disease risk 2016-2017.

Chepkorir E1,2, Tchouassi DP3, Konongoi SL4, Lutomiah J4, Tigoi C3, Irura Z5, Eyase F6, Venter M7, Sang R3.

Author information: 1 International Centre of Insect Physiology and Ecology, P. O. Box 30772-00100, Nairobi, Kenya. echepkorir@icipe.org. 2 Center for Viral Zoonoses, Department of Medical Virology, University of Pretoria, P. O. Box 323, Arcadia, 0007, South Africa. echepkorir@icipe.org. 3 International Centre of Insect Physiology and Ecology, P. O. Box 30772-00100, Nairobi, Kenya. 4 Center for Virus Research, Kenya Medical Research Institute, P. O. Box 54628-00200, Nairobi, Kenya. 5 Division of Disease Surveillance and Response, Ministry of Health, P. O. Box 20781-00202, Nairobi, Kenya. 6 Jomo Kenyatta University of Agriculture and Technology, P.O. Box 606, Village Market, Nairobi, Kenya. 7 Center for Viral Zoonoses, Department of Medical Virology, University of Pretoria, P. O. Box 323, Arcadia, 0007, South Africa.




Yellow fever, Dengue, West Nile and Zika viruses are re-emerging mosquito-borne Flaviviruses of public health concern. However, the extent of human exposure to these viruses and associated disease burden in Kenya and Africa at large remains unknown. We assessed the seroprevalence of Yellow fever and other Flaviviruses in human populations in West Pokot and Turkana Counties of Kenya. These areas border Uganda, South Sudan and Ethiopia where recent outbreaks of Yellow fever and Dengue have been reported, with possibility of spillover to Kenya.


Human serum samples collected through a cross-sectional survey in West Pokot and Turkana Counties were screened for neutralizing antibodies to Yellow fever, Dengue-2, West Nile and Zika virus using the Plaque Reduction Neutralization Test (PRNT). Seroprevalence was compared by county, site and important human demographic characteristics. Adjusted odds ratios (aOR) were estimated using Firth logistic regression model.


Of 877 samples tested, 127 neutralized with at least one of the four flaviviruses (14.5, 95% CI 12.3-17.0%), with a higher proportion in Turkana (21.1%, n = 87/413) than in West Pokot (8.6%, n = 40/464). Zika virus seroprevalence was significantly higher in West Pokot (7.11%) than in Turkana County (0.24%; χ2 P < 0.0001). A significantly higher Yellow fever virus seroprevalence was also observed in Turkana (10.7%) compared to West Pokot (1.29%; χ2 P < 0.0001). A high prevalence of West Nile virus was detected in Turkana County only (10.2%) while Dengue was only detected in one sample, from West Pokot. The odds of infection with West Nile virus was significantly higher in males than in females (aOR = 2.55, 95% CI 1.22-5.34). Similarly, the risk of Zika virus infection in West Pokot was twice higher in males than females (aOR = 2.01, 95% CI 0.91-4.41).


Evidence of neutralizing antibodies to West Nile and Zika viruses indicates that they have been circulating undetected in human populations in these areas. While the observed Yellow Fever prevalence in Turkana and West Pokot Counties may imply virus activity, we speculate that this could also be as a result of vaccination following the Yellow Fever outbreak in the Omo river valley, South Sudan and Uganda across the border.

KEYWORDS: Dengue virus; Flaviviruses risk assessment; Northern Kenya; Plaque reduction neutralization test; Seroprevalence; West Nile virus; Yellow fever virus; Zika virus

PMID: 31101058 DOI: 10.1186/s12985-019-1176-y

Keywords: Flavivirus; WNV; Zika Virus; Dengue Fever; Yellow Fever; Serology; Seroprevalence; Kenya.