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Yellow fever virus (YFV) continues to cause periodic outbreaks of severe disease throughout tropical regions of South America and Africa despite the availability of an effective vaccine. Despite efforts to control this virus for the last century, no antivirals have been approved for the treatment of YFV. The purpose of this study was to evaluate the broadly active antiviral compound remdesivir (RDV) in a hamster model of disease. Yellow fever (YF) disease in hamsters was prevented when treatment with RDV was initiated just prior to virus challenge, which was confirmed in a second study. Disease parameters including viremia, serum ALT and weight loss were significantly improved with RDV treatment in a dose-dependent manner. RDV was also effective when treatment was initiated as late as 4 days post-virus infection (dpi). These results demonstrate therapeutic efficacy of RDV in the treatment of YF in a relevant animal model of disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The pretravel management of the international pediatric traveler is based on provision of preventive education, chemoprophylaxis against malaria and traveler's diarrhea, as well as travel vaccinations. Immunization requirements are determined based on the traveler's pretravel immunization status, age, medical history, and destination. Immunization needs also vary depending on the exposures during the trip. Potential exposure to water, insects, or animals as well as duration of travel will help tailor risk avoidance education and travel immunizations. This review provides clinicians an overview of vaccines recommended for children traveling internationally., Competing Interests: Disclosure The author denies any conflict of interest or relationship with a commercial company that has a direct financial interest in subject matter of materials discussed in this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Childhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic., Methods: We used two to three models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption)., Results: Reduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increase the risk of measles outbreaks (both countries did complete their supplementary immunisation activities (SIAs) planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people per year until the campaigns are implemented. For meningococcal A vaccination, short-term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1- to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns., Conclusions: The impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination., Funding: Bill and Melinda Gates Foundation and Gavi, the Vaccine Alliance., Competing Interests: KG, KA, JH, AK, KW, XL, SE, MF, KM, TP No competing interests declared, NT NT is an employee of the Institute for Disease Modeling at the Bill & Melinda Gates Foundation, which funded the research. MJ KM is an employee of the Institute for Disease Modeling at the Bill & Melinda Gates Foundation, which funded the research. CT CT declares a consultancy fee from GSK in 2018 (unrelated to the submitted work). MJ Reviewing editor, eLife, (© 2021, Gaythorpe et al.)

Yellow fever (YF) is a viral, vector-borne, haemorrhagic fever endemic in tropical regions of Africa and South America. The vaccine for YF is considered safe and effective, but intervention strategies need to be optimised; one of the tools for this is mathematical modelling. We refine and expand an existing modelling framework for Africa to account for transmission in South America. We fit to YF occurrence and serology data. We then estimate the subnational forces of infection for the entire endemic region. Finally, using demographic and vaccination data, we examine the impact of vaccination activities. We estimate that there were 109,000 (95% credible interval [CrI] [67,000-173,000]) severe infections and 51,000 (95% CrI [31,000-82,000]) deaths due to YF in Africa and South America in 2018. We find that mass vaccination activities in Africa reduced deaths by 47% (95% CrI [10%-77%]). This methodology allows us to evaluate the effectiveness of vaccination and illustrates the need for continued vigilance and surveillance of YF., Competing Interests: KG, AH, KJ, DG, LC, TG, NF No competing interests declared, (© 2021, Gaythorpe et al.)

Combined cellular and humoral host immune response determine the clinical course of a viral infection and effectiveness of vaccination, but currently the cellular immune response cannot be measured on simple blood samples. As functional activity of immune cells is determined by coordinated activity of signaling pathways, we developed mRNA-based JAK-STAT signaling pathway activity assays to quantitatively measure the cellular immune response on Affymetrix expression microarray data of various types of blood samples from virally infected patients (influenza, RSV, dengue, yellow fever, rotavirus) or vaccinated individuals, and to determine vaccine immunogenicity. JAK-STAT1/2 pathway activity was increased in blood samples of patients with viral, but not bacterial, infection and was higher in influenza compared to RSV-infected patients, reflecting known differences in immunogenicity. High JAK-STAT3 pathway activity was associated with more severe RSV infection. In contrast to inactivated influenza virus vaccine, live yellow fever vaccine did induce JAK-STAT1/2 pathway activity in blood samples, indicating superior immunogenicity. Normal (healthy) JAK-STAT1/2 pathway activity was established, enabling assay interpretation without the need for a reference sample. The JAK-STAT pathway assays enable measurement of cellular immune response for prognosis, therapy stratification, vaccine development, and clinical testing., (Copyright © 2020 Bouwman, Verhaegh, Holtzer and van de Stolpe.)

Introduction: Although effective live attenuated yellow fever (YF) vaccines have been available for over 9 decades sporadic outbreaks continue to occur in endemic regions. These may be linked to several factors including epidemiological factors such as vector and intermediate host distribution or vaccine coverage and efficacy. The World Health Organization's research priorities include gathering systematic evidence around the potential need for booster vaccination with YF vaccine whether this follows full or fractional doses in children. Knowledge on the longevity of response to YF vaccine and the implications of this response needs to be consolidated to guide future vaccination policy. Methods: We measured anti-YF IgG by microneutralization assay in a group of 481 African infants who had received YF vaccine as part of routine EPI programmes, to explore serological protection from YF 5-6 years post YF vaccination, as well as the effect of co variates. Findings: Notably, 22.2% of the cohort had undetectable antibody concentrations, with another 7.5% revealing concentrations below the threshold of seropositivity of 0.5 IU/mL. Sex, season, country and time since vaccination did not affect the longevity of antibody concentration or having antibody concentrations above a defined threshold. Conclusion: Roughly 30% of children in this cohort did not demonstrate anti-yellow fever antibody concentrations above the defined threshold of protection, with 20% having no demonstrable antibody. Knowledge on the longevity of response to YF vaccine and the implications needs to be consolidated to guide future vaccination policy., (Copyright © 2020 Idoko, Domingo, Tapia, Sow, Geldmacher, Saathoff and Kampmann.)

Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil). Included patients were referred for planned vaccination by a rheumatologist; in remission, or with low disease activity; and had low level immunosuppression or the attending physician advised interruption of immunosuppression for safety reasons. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, and 17DD-YF viremia were evaluated at various time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). Individuals evaluated ( n = 278), including patients with rheumatoid arthritis (RA; 79), spondyloarthritis (SpA; 59), systemic sclerosis (8), systemic lupus erythematosus (SLE; 27), primary Sjögren's syndrome (SS; 54), and healthy controls (HC; 51). Only mild AE were reported. The frequency of local and systemic AE in patients with AID and HC did not differ significantly (8 vs. 10% and 21 vs. 32%; p = 1.00 and 0.18, respectively). Patients with AID presented late seroconversion profiles according to kinetic timelines of the plaque reduction neutralization test (PRNT). PRNT-determined virus titers (copies/mL) [181 (95% confidence interval (CI), 144-228) vs. 440 (95% CI, 291-665), p = 0.004] and seropositivity rate (78 vs. 96%, p = 0.01) were lower in patients with AID after 28 days, particularly those with SpA (73%) and SLE (73%), relative to HC. The YF viremia peak (RNAnemia) was 5-6 days after vaccination in all groups. In conclusion, consistent seroconversion rates were observed in patients with AID and our findings support that planned 17DD-YF primary vaccination is safe and immunogenic in patients with AID., (Copyright © 2020 Valim, Machado, Miyamoto, Pinto, Rocha, Serrano, Dinis, Gouvêa, Dias, Campi-Azevedo, Teixeira-Carvalho, Peruhype-Magalhães, Costa-Rocha, Lima, Miranda, Trindade, Maia, Gavi, Silva, Duque, Gianordoli, Casagrande, Oliveira, Moura, Nicole-Batista, Rodrigues, Clemente, Magalhães, Bissoli, Gouvea, Pinto-Neto, Costa, Giovelli, Brandão, Polito, Koehlert, Borjaille, Pereira, Dias, Merlo, Genelhu, Pretti, Giacomin, Burian, Fantinato, Pileggi, Mota and Martins-Filho.)

Yellow fever (YF) is a vaccine-preventable disease, but live attenuated YF vaccine (YFV) is contraindicated in immunosuppressed patients due to the risk of life-threatening YFV-associated side effects. This study aimed to evaluate 1. the knowledge of renal transplant recipients (RTRs) about the contraindication and risks of YFV; 2. the prevalence of inadvertent vaccination of RTRs against YF; and 3. the outcome of these patients. A cross-sectional telephone contact study was conducted with 200 RTRs selected from the outpatient clinic of our transplantation unit. There were 116 successful telephone contacts (58%). A total of 11 vaccinated patients were identified: 5 received YFV in the pretransplant period and 6 in the post-transplant period. All patients received the full dose of the vaccine. Among those vaccinated after transplant, only 1 reported a mild adverse event (nausea) after receiving the vaccine. All vaccinated patients who were post-transplant did not know about vaccine contraindications as a result of their clinical condition. Among the unvaccinated patients, this rate was 12.4%. YFV is the main tool for disease prevention and control as there is no specific antiviral treatment for YF. Our results confirm the evidence that transplant recipients tolerate YFV well. However, data are not strong enough to recommend this vaccine in transplant recipients. Counseling RTRs on the contraindications of YFV is important to prevent inadvertent use of this vaccine in this population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The recent Zika virus (ZIKV) epidemic in the Americas, followed by the yellow fever virus (YFV) outbreaks in Angola and Brazil highlight the urgent need for safe and efficient vaccines against the ZIKV as well as much greater production capacity for the YFV-17D vaccine. Given that the ZIKV and the YFV are largely prevalent in the same geographical areas, vaccines that would provide dual protection against both pathogens may obviously offer a significant benefit. We have recently engineered a chimeric vaccine candidate (YF-ZIKprM/E) by swapping the sequences encoding the YFV-17D surface glycoproteins prM/E by the corresponding sequences of the ZIKV. A single vaccine dose of YF-ZIKprM/E conferred complete protection against a lethal challenge with wild-type ZIKV strains. Surprisingly, this vaccine candidate also efficiently protected against lethal YFV challenge in various mouse models. We demonstrate that CD8 + but not CD4 + T cells, nor ZIKV neutralizing antibodies are required to confer protection against YFV. The chimeric YF-ZIKprM/E vaccine may thus be considered as a dual vaccine candidate efficiently protecting mice against both the ZIKV and the YFV, and this following a single dose immunization. Our finding may be particularly important in the rational design of vaccination strategies against flaviviruses, in particular in areas where YFV and ZIKV co-circulate.

Live 17D is widely used as a prophylactic vaccine strain for yellow fever virus that induces potent neutralizing humoral and cellular immunity against the wild-type pathogen. 17D replicates and kills mouse and human tumor cell lines but not non-transformed human cells. Intratumoral injections with viable 17D markedly delay transplanted tumor progression in a CD8 T-cell-dependent manner. In mice bearing bilateral tumors in which only one is intratumorally injected, contralateral therapeutic effects are observed consistent with more prominent CD8 T-cell infiltrates and a treatment-related reduction of Tregs. Additive efficacy effects were observed upon co-treatment with intratumoral 17D and systemic anti-CD137 and anti-PD-1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized with 17D, intratumoral 17D treatment achieved better local and distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8 T-cell infiltration in the treated tumor. The repurposed use of a GMP-grade vaccine to be given via the intratumoral route in prevaccinated patients constitutes a clinically feasible and safe immunotherapy approach., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Objectives: To evaluate the public health benefits and economic value of live-attenuated yellow fever (YF) 17D vaccine in Colombia., Methods: A decision tree model was used to assess the theoretical impact of routine YF vaccination of 1-year-olds (no "catch-up") during the interepidemic period from 1980 to 2002, avoiding capturing the impact of YF vaccine introduction in 2003. The vaccine was assumed to be 99% effective, to provide lifetime protection, and to cover 85% of the target population. Costs per disability-adjusted life-year (DALY) averted were computed from payer and societal perspectives. Univariate sensitivity analyses were performed., Results: During the interepidemic period, routine YF vaccination would have averted 2223 nonfatal cases of YF and 65 deaths, leading to an overall reduction of 1365 DALYs. The net cost of this vaccination would have been $25 964 813 (payer's perspective) and $16 535 465 (societal perspective). Cost per DALY averted was $19 022 and $12 114 from payer and societal perspectives, respectively (all costs in 2015 US dollars). Vaccination was considered cost-effective from both perspectives (ie, between 1- and 3-fold the gross domestic product per capita, $7158) and remains so if price per dose was $2.75 or less and $4.66 from payer and societal perspectives, respectively. Underreporting had the largest impact on the results., Conclusions: Routine toddler YF vaccination in Colombia would have been considered cost-effective in the prevaccination era. This study provides insights on the value of vaccination in an upper middle-income country., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Yellow fever is a serious disease caused by infection with the yellow fever virus (YFV). A live-attenuated YFV vaccine strain, 17D (YFV-17D) is the only virus strain available for the production of the YFV vaccine. This study evaluated the immunogenicity and immune persistence of vaccination with YFV-17D and identified their influencing factors in Chinese peacekeepers deployed to Africa. Serum specimens were collected before and ≥21 days after primary vaccination with YFV-17D in 349 Chinese peacekeepers who were subsequently deployed to Africa for the first time from 2016 to 2017 (population 1). Serum specimens were collected from 1 to 11 years after vaccination with YFV-17D in 2062 returned Chinese peacekeepers who were deployed to Africa from 2005 to 2015 (population 2). We found that YFV-17D exhibited an excellent protective effect in the Chinese peacekeepers deployed to Africa early following vaccination. In the Chinese peacekeepers one year after vaccination, the serum antibody titer against YFV increased with increasing age at vaccination; in those two or more years after vaccination, the serum antibody titer against YFV decreased over years and was similar to but greater than the minimum protective level 11 years after vaccination. The number of peacekeeping missions exhibited an almost negligible influence on the serum antibody titer against YFV. (This study has been registered at International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/) under registration Nos. ChiCTR1800017024.)., (Copyright © 2018. Published by Elsevier B.V.)

Background: Although a safe and effective yellow fever vaccine was developed more than 80 years ago, several issues regarding its use remain unclear. For example, what is the minimum dose that can provide immunity against the disease? A useful tool that can help researchers answer this and other related questions is a computational simulator that implements a mathematical model describing the human immune response to vaccination against yellow fever., Methods: This work uses a system of ten ordinary differential equations to represent a few important populations in the response process generated by the body after vaccination. The main populations include viruses, APCs, CD8+ T cells, short-lived and long-lived plasma cells, B cells and antibodies., Results: In order to qualitatively validate our model, four experiments were carried out, and their computational results were compared to experimental data obtained from the literature. The four experiments were: a) simulation of a scenario in which an individual was vaccinated against yellow fever for the first time; b) simulation of a booster dose ten years after the first dose; c) simulation of the immune response to the yellow fever vaccine in individuals with different levels of naïve CD8+ T cells; and d) simulation of the immune response to distinct doses of the yellow fever vaccine., Conclusions: This work shows that the simulator was able to qualitatively reproduce some of the experimental results reported in the literature, such as the amount of antibodies and viremia throughout time, as well as to reproduce other behaviors of the immune response reported in the literature, such as those that occur after a booster dose of the vaccine.

Background: A yellow fever epidemic occurred in Angola in 2016 with 884 laboratory confirmed cases and 373 deaths. Eleven unvaccinated Chinese nationals working in Angola were also infected and imported the disease to China, thereby presenting the first importation of yellow fever into Asia. In Angola, there are about 259,000 Chinese foreign workers. The fact that 11 unvaccinated Chinese workers acquired yellow fever suggests that many more Chinese workers in Angola were not vaccinated., Methods: We applied a previously developed model to back-calculate the number of unvaccinated Chinese workers in Angola in order to determine the extent of lack of vaccine coverage., Results: Our models suggest that none of the 259,000 Chinese had been vaccinated, although yellow fever vaccination is mandated by the International Health Regulations., Conclusion: Governments around the world including China need to ensure that their citizens obtain YF vaccination when traveling to countries where such vaccines are required in order to prevent the international spread of yellow fever.

Mosquitos are responsible for a number of protozoal and viral diseases. Malaria, dengue, Japanese encephalitis (JE) and chikungunya epidemics occur commonly all over the world, leading to marked mortality and morbidity in children. Zika, Yellow fever and West Nile fever are others requiring prevention. Environmental control and mosquito bite prevention are useful in decreasing the burden of disease but vaccination has been found to be most cost-effective and is the need of the hour. RTS,S/AS01 vaccine is the first malaria vaccine being licensed for use against P. falciparum malaria. Dengvaxia (CYD-TDV) against dengue was licensed first in Mexico in 2015. A Vero-cell derived, inactivated and alum-adjuvanted JE vaccine based on the SA14-14-2 strain was approved in 2009 in North America, Australia and various European countries. It can be used from 2 mo of age. In India, immunization is carried out in endemic regions at 1 y of age. Another inactivated Vero-cell culture derived Kolar strain, 821564XY, JE vaccine is being used in India. Candidate vaccines against dengue, chikungunya and West Nile fever are been discussed. A continued research and development of new vaccines are required for controlling these mosquito-borne diseases.

Yellow fever (YF) is a viral disease transmitted by mosquitoes and endemic mostly in South America and Africa with 20-50% fatality. All current licensed YF vaccines, including YF-Vax ® (Sanofi-Pasteur, Lyon, France) and 17DD-YFV (Bio-Manguinhos, Rio de Janeiro, Brazil), are based on live attenuated virus produced in hens' eggs and have been widely used. The YF vaccines are considered safe and highly effective. However, a recent increase in demand for YF vaccines and reports of rare cases of YF vaccine-associated fatal adverse events have provoked interest in developing a safer YF vaccine that can be easily scaled up to meet this increased global demand. To this point, we have engineered the YF virus envelope protein (YFE) and transiently expressed it in Nicotiana benthamiana as a stand-alone protein (YFE) or as fusion to the bacterial enzyme lichenase (YFE-LicKM). Immunogenicity and challenge studies in mice demonstrated that both YFE and YFE-LicKM elicited virus neutralizing (VN) antibodies and protected over 70% of mice from lethal challenge infection. Furthermore, these two YFE-based vaccine candidates induced VN antibody responses with high serum avidity in nonhuman primates and these VN antibody responses were further enhanced after challenge infection with the 17DD strain of YF virus. These results demonstrate partial protective efficacy in mice of YFE-based subunit vaccines expressed in N. benthamiana . However, their efficacy is inferior to that of the live attenuated 17DD vaccine, indicating that formulation development, such as incorporating a more suitable adjuvant, may be required for product development.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts, meets 3 times per year to develop recommendations for vaccine use in the United States. The group has 15 voting members, and each member's term is 4 years. ACIP members and Centers for Disease Control and Prevention (CDC) staff discuss the epidemiology of vaccine-preventable diseases and vaccine research, effectiveness, safety data, and clinical trial results. Representatives from the American Academy of Pediatrics (Carrie L. Byington and D. W. K.) and the Pediatric Infectious Diseases Society (S. T. O.) are present as liaisons to the ACIP. The ACIP met on June 21 to 22, 2017, to discuss catch-up vaccination for hepatitis A vaccine, influenza surveillance, influenza vaccine effectiveness, herpes zoster vaccine, the effect of varicella vaccination on the incidence of herpes zoster, meningococcal disease in patients taking eculizumab, and considerations for a potential third dose of measles, mumps, and rubella (MMR) vaccine to combat ongoing mumps outbreaks. Updates on dengue virus epidemiology, Zika virus vaccines, anthrax vaccine, yellow fever vaccine, and the Vaccine Adverse Event Reporting System were given also., (© The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite the availability of a safe and efficacious yellow fever vaccine since 1937, yellow fever remains a public health threat as a re-emerging disease in Africa and South America. We reviewed the trend of reported yellow fever outbreaks in eastern African countries, identified the risk epidemiological factors associated with the outbreaks and assessed the current situation of Yellow Fever vaccination in Africa. Surveillance and case finding for yellow fever in Africa are insufficient primarily due to lack of appropriate diagnostic capabilities, poor health infrastructure resulting in under-recognition, underreporting and underestimation of the disease. Despite these challenges, Ethiopia reported 302,614 cases (30,505 deaths) in 1943-2015, Kenya had 207 cases (38 deaths) in 1992-2016, Sudan experienced 31,750 suspected cases (1855 deaths) from 1940 to 2012 and Uganda had 452 cases (65 deaths) in 1941-2016. Major risk factors associated with past yellow fever outbreaks include climate, human practices and virus genetics. Comparisons between isolates from different outbreaks after 45 years have revealed the genetic stability of the structural proteins of YFV which are the primary targets of the host immune cells. This probably explains why yellow fever 17D vaccine is considered as outstandingly efficacious and safe after being used for 75 years. However, the 14 amino-acid changes among these isolates may have a greater impact on the changing disease epidemiology, virulence and transmission rate. Low population immunity against YF influences outbreak frequency especially in countries where the incorporation of YF vaccination is not combined with mass vaccination campaigns or vaccination is limited to international travellers. Understanding Yellow fever virus epidemiology as determined by its evolution underscores appropriate disease mitigation strategies and immunization policies. Mobilizing scarce resources to enhance population immunity through sufficient vaccination, promoting environmental sanitation/hygienic practices, driving behavioral change and community-based vector control are significant to preventing future epidemics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

States in south-eastern Brazil were recently affected by the largest Yellow Fever (YF) outbreak seen in a decade in Latin America. Here we provide a quantitative assessment of the risk of travel-related international spread of YF indicating that the United States, Argentina, Uruguay, Spain, Italy and Germany may have received at least one travel-related YF case capable of seeding local transmission. Mitigating the risk of imported YF cases seeding local transmission requires heightened surveillance globally., (This article is copyright of The Authors, 2017.)

Background: In addition to protection against the target diseases, vaccines may have non-specific effects (NSEs). Measles vaccine (MV) has beneficial NSEs, providing protection against non-measles deaths, most so for girls. By contrast, though protecting against diphtheria, tetanus and pertussis, DTP vaccine is associated with increased female mortality relative to male mortality. In 2008, Guinea-Bissau replaced DTP with the DTP-containing pentavalent vaccine (Penta; DTP-H. influenza type B-Hepatitis B) at 6, 10 and 14weeks and yellow fever vaccine (YF) was to be given with MV. We investigated possible sex-differential mortality rates following Penta and MV+YF vaccination., Methods: Bandim Health Project (BHP) registers vaccines given by the three government health centres in the study area and vital status through demographic surveillance. We assessed the association between sex and mortality by vaccination status in Cox proportional hazards models with age as underlying timescale. Follow-up was censored at a subsequent vaccination contact or after 6months of follow-up., Results: Between September 2008 and April 2011, we registered 23,448 vaccination contacts for children aged 42-365days; 17,313 were for Penta and 3028 for MV (2907 co-administered with YF). During follow-up 112 children died. The female/male mortality rate ratio was 1.73 (1.11-2.70) following Penta and 0.38 (0.12-1.19) after MV (p=0.02 for same effect). Adjusting for maternal education or weight-for-age at the time of vaccination did not change the estimates., Conclusion: Penta appears to have the same negative effects on mortality as those seen for DTP. Assessing post-vaccination mortality for boys and girls is necessary to improve the vaccination programme., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The 17D-yellow fever (YF) vaccination is considered contraindicated in immune-compromised patients; however, accidental vaccination occurs. In this population, measuring the immune response is useful in clinical practice., Methods: In this study we compare two antibody tests (the Immune Fluorescence Assay and the Plaque Reduction Neutralization Test) in a group of Dutch immune-compromised travellers with a median of 33 days (IQR [28-49]) after primary YF vaccination., Results: We collected samples of 15 immune-compromised vaccinees vaccinated with the 17D yellow fever vaccine between 2004 and 2012. All samples measured in the plaque reduction neutralization test yielded positive results (>80% virus neutralization with a 1:10 serum dilution). Immune Fluorescence Assay sensitivity was 28% (95% CI [0.12-0.49]). No adverse events were reported., Conclusions: All immune-compromised patients mounted an adequate response with protective levels of virus neutralizing antibodies to the 17-D YF vaccine. No adverse effects were reported. Compared to the plaque reduction neutralization test, the sensitivity of the Immune Fluorescence Assay test was low. Further research is needed to ascertain that 17D vaccination in immune-compromised patients is safe., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Travelers receive medical advice from a variety of sources, including travel agencies. The aim of this study is to describe the quality of pre-travel advice provided by travel agencies in Cuzco to travelers interested in visiting malaria and yellow fever endemic areas., Methods: Trained medical students posed as tourists and visited travel agencies in Cuzco requesting travel advice for a trip to the southern Amazon of Peru, recording advice regarding risk and prevention of malaria and yellow fever., Results: A total of 163 registered travel agencies were included in the study. The mean proposed tour duration was 6.8 days (±1.4 days) with a median time to departure of 3 days and a median tour cost of 805 US dollars (USD) [interquartile range (IQR) 580-1,095]. Overall, 45% employees failed to mention the risk for any illness. Eighteen percent of the employees acknowledged risk of malaria and 53% risk of yellow fever. However, 36% denied malaria risk and 2% denied risk of yellow fever in the region. The price of tours from travel agencies that did not mention any health risk was significantly lower [1,009.6 ± 500.5 vs 783.9 ± 402 USD, t (152) = 3, p < 0.01] compared with the price from agencies that did mention health risks. Almost all who acknowledged malaria (97%) and/or yellow fever (100%) were able to provide at least one recommendation for prevention. However, advice was not always accurate or spontaneously volunteered. Only 7% of the employees provided both correct scheduling and location information for administration of the yellow fever vaccine., Conclusions: The majority of registered travel agencies in Cuzco did not provide sufficient and accurate information regarding risk and prevention of malaria and yellow fever to travelers inquiring about trips to the southern Amazon of Peru., (© 2014 International Society of Travel Medicine.)

Introduction: Available scientific evidence to recommend or to advise against booster doses of yellow fever vaccine (YFV) is inconclusive. A study to estimate the seropositivity rate and geometric mean titres (GMT) of adults with varied times of vaccination was aimed to provide elements to revise the need and the timing of revaccination., Methods: Adults from the cities of Rio de Janeiro and Alfenas located in non-endemic areas in the Southeast of Brazil, who had one dose of YFV, were tested for YF neutralising antibodies and dengue IgG. Time (in years) since vaccination was based on immunisation cards and other reliable records., Results: From 2011 to 2012 we recruited 691 subjects (73% males), aged 18-83 years. Time since vaccination ranged from 30 days to 18 years. Seropositivity rates (95%C.I.) and GMT (International Units/mL; 95%C.I.) decreased with time since vaccination: 93% (88-96%), 8.8 (7.0-10.9) IU/mL for newly vaccinated; 94% (88-97), 3.0 (2.5-3.6) IU/mL after 1-4 years; 83% (74-90), 2.2 (1.7-2.8) IU/mL after 5-9 years; 76% (68-83), 1.7 (1.4-2.0) IU/mL after 10-11 years; and 85% (80-90), 2.1 (1.7-2.5) IU/mL after 12 years or more. YF seropositivity rates were not affected by previous dengue infection., Conclusions: Eventhough serological correlates of protection for yellow fever are unknown, seronegativity in vaccinated subjects may indicate primary immunisation failure, or waning of immunity to levels below the protection threshold. Immunogenicity of YFV under routine conditions of immunisation services is likely to be lower than in controlled studies. Moreover, infants and toddlers, who comprise the main target group in YF endemic regions, and populations with high HIV infection rates, respond to YFV with lower antibody levels. In those settings one booster dose, preferably sooner than currently recommended, seems to be necessary to ensure longer protection for all vaccinees., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Indication for yellow fever vaccination is not always easy to assess. The decision to immunize is not only based on the actual risk of the disease in a specific location, but also on public health considerations in the visited country (in order to respectively avoid epidemics in endemic countries or the introduction of the virus in zones where the vectors mosquitoes are present) and on travelers' risk factors for severe or even fatal vaccine adverse events. WHO has recently published new recommendations regarding vaccination against yellow fever after concluding that one dose of vaccine generates a life-long protection. This article tends to clarify the strategy to adopt in 2013 using cases frequently encountered in the practice of travel medicine.

Several risk groups are known for the rare but serious, frequently fatal, viscerotropic reactions following live yellow fever virus vaccine (YEL-AVD). Establishing additional risk groups is hampered by ignorance of the numbers of vaccinees in factor-specific risk groups thus preventing their use as denominators in odds ratios (ORs). Here, we use an equation to calculate ORs using the prevalence of the factor-specific risk group in the population who remain well. The 95% confidence limits and P values can also be calculated. Moreover, if the estimate of the prevalence is imprecise, discrimination analysis can indicate the prevalence at which the confidence interval results in an OR of ∼1 revealing if the prevalence might be higher without yielding a non-significant result. These methods confirm some potential risk groups for YEL-AVD and cast doubt on another. They should prove useful in situations in which factor-specific risk group denominator data are not available.

The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were no adverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. More research is needed on possible adverse effects of concurrent administration of yellow fever vaccine and methotrexate to determine the potential of this method for more frequent use.

Objective: To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy., Methods: All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self-administered standardized questionnaire within 10 days after immunization. YF-specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids., Results: Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination., Conclusion: After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale studies are needed to confirm these results., (Copyright © 2013 by the American College of Rheumatology.)

Background: Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections., Discussion: Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues.Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system.HERV-K expression has been detected in different types of tumors.Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family.The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression.The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder and breast cancer. An amino acid sequence similar to HERV-K-MEL, recognized to cause a significant protective effect against melanoma, is shared by the antigenic determinants expressed by some vaccines such as BCG, vaccinia virus and the yellow fever virus.HERV-K are also reactivated in the majority of human breast cancers. Monoclonal and single-chain antibodies against the HERV-K Env protein recently proved capable of blocking the proliferation of human breast cancer cells in vitro, inhibiting tumor growth in mice bearing xenograft tumors., Summary: A recent epidemiological study provided provisional evidence of how melanoma risk could possibly be reduced if the yellow fever virus vaccine (YFV) were received at least 10 years before, possibly preventing tumor initiation rather than culling melanoma cells already compromised. Further research is recommended to confirm the temporal pattern of this protection and eliminate/attenuate the potential role of relevant confounders as socio-economic status and other vaccinations.It appears also appropriate to examine the potential protective effect of YFV against other malignancies expressing high levels of HERV-K antigens, namely breast cancer, sarcoma, lymphoma and bladder cancer.Tumor immune-therapy, as described for the monoclonal antibodies against breast cancer, is indeed considered more complex and less advantageous than immune-prevention. Cellular immunity possibly triggered by vaccines as for YFV might also be involved in anti-cancer response, in addition to humoral immunity.

Background: The National Travel Health Network and Centre (NaTHNaC) introduced a program of registration, training, standards, and audit for yellow fever vaccination centers (YFVCs) in England, Wales, and Northern Ireland (EWNI) in 2005. Prior to rolling out the program, NaTHNaC surveyed YFVCs in England., Objectives: To reassess the practice of YFVCs in 2009, 4 years after the institution of the NaTHNaC program, to identify areas for ongoing support, and to assess the impact of the program., Methods: In 2009, all YFVCs in EWNI were asked to complete a questionnaire on type of practice, administration of travel vaccines, staff training, vaccine storage and patient record keeping, use of travel health information, evaluation of NaTHNaC yellow fever (YF) training, and resource and training needs. Data were analyzed using Microsoft Excel® and STATA 9®., Results: The questionnaire was completed by 1,438 YFVCs (41.5% of 3,465 YFVCs). Most YFVCs were based in General Practice (87.4%). In nearly all YFVCs (97.0%), nurses advised travelers and administered YF vaccine. An annual median of 50 doses of YF vaccine was given by each YFVC. A total of 96.7% of nurses had received training in travel medicine, often through study days run by vaccine manufacturers. The internet was frequently used for information during travel consultations (84.8%) and NaTHNaC's on-line and telephone advice resources were highly rated. Following YF training, 95.8% of attendees expressed improved confidence regarding YF vaccination issues. There was excellent adherence to vaccination standards: ≥ 94% correctly stored vaccines, recorded refrigerator temperatures, and maintained YF vaccination records., Conclusions: In the 4 years since institution of the NaTHNaC program for YFVCs, there has been improved adherence to basic standards of immunization practice and increased confidence of health professionals in YF vaccination. The NaTHNaC program could be a model for other national public health bodies, as they establish a program for YF centers., (© 2012 International Society of Travel Medicine.)

Concerns exist about the serologic response to yellow fever (YF) vaccine when given within 28 days of another live virus vaccine. We report the case of a healthy adult who received 17D YF vaccine 21 days following administration of another live viral vaccine, and developed a protective level of immunity against YF virus., (© 2012 International Society of Travel Medicine.)

Background: Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable., Methodology/principal Findings: A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5) TCID(50). Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles., Conclusions/significance: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

At the beginning of 21 century endemic areas of yellow fever are in tropical forests of Africa and South America, covering 43 countries of the around the world. In a period of 11 years 2005 citizens from 14 countries of Africa and 871 citizens from 8 countries of South America were taken ill with of a yellow fever. On the both continentals were observed distinct, limited (no more than 40 people) ictuses of urban of a yellow fever related to mosquito Aedes aegypti. Still, the total mortality is high--up to 35%. The systems of epidemiological surveillance and informational connection are created; the live vaccine in sufficient amount for general is delivered to the hot spots of disease. Civil wars and ethnic conflicts hinder the introduction of compulsory vaccination in national calendars of the inoculation of children in endemic countries. Because of it the vaccination is realized slowly: nowadays the vaccination is introduce in 19 among 25 countries of Africa with high risk of disease.

Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of intestinal homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult to reconcile with reports of intestinal T cell responses after alternative routes of immunization. We reconcile this discrepancy by demonstrating that activation within spleen results in intermediate induction of homing potential to the intestinal mucosa. We further demonstrate that memory T cells within small intestine epithelium do not routinely recirculate with memory T cells in other tissues, and we provide evidence that homing is similarly dynamic in humans after subcutaneous live yellow fever vaccine immunization. These data explain why systemic immunization routes induce local cell-mediated immunity within the intestine and indicate that this tissue must be seeded with memory T cell precursors shortly after activation.