BACKGROUND: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years.
METHODS: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA.
RESULTS: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD).
CONCLUSIONS: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

Free-ranging non-human primates (NHP) can live in anthropized areas or urban environments in close contact with human populations. This condition can enable the emergence and transmission of high-impact zoonotic pathogens. For the first time, we detected a coinfection of the yellow fever (YF) virus with Toxoplasma gondii in a free-ranging NHP in a highly urbanized area of a metropolis in Brazil. Specifically, we observed this coinfection in a black-tufted marmoset found dead and taken for a necropsy by the local health surveillance service. After conducting an epidemiological investigation, characterizing the pathological features, and performing molecular assays, we confirmed that the marmoset developed an acute fatal infection caused by T. gondii in coinfection with a new YF virus South American-1 sub-lineage. As a result, we have raised concerns about the public health implications of these findings and discussed the importance of diagnosis and surveillance of zoonotic agents in urbanized NHPs. As competent hosts of zoonotic diseases such as YF and environmental sentinels for toxoplasmosis, NHPs play a crucial role in the One Health framework to predict and prevent the emergence of dangerous human pathogens.

Yellow fever vaccine-associated neurotropic disease (YEL-AND) is a rare and serious complication following vaccination with the 17D live attenuated yellow fever vaccine. Cases of YEL-AND have presented as acute inflammatory demyelinating polyneuropathy, acute disseminated encephalomyelitis, and meningoencephalitis. To date, intracranial imaging of the progression and resolution of this disease has been minimally depicted in the literature. We present the case of a 67-year-old woman who developed YEL-AND following vaccination. Her diagnosis was complicated by imaging findings consistent with variant Creutzfeldt Jakob Disease. Her clinical history and the progression of her intracranial imaging is discussed in this case report.

Yellow fever (YF) is a viral haemorrhagic fever caused by yellow fever virus transmitted by Aedes mosquitoes. Since 2013, in Chad, four cases of yellow fever have been detected and confirmed as part of the national fever surveillance program. We here report the last clinical case confirmed in the health district of Lai. The patient was a 57-year-old man with no significant medical and surgical history and unknown immunisation status. He consulted on April 21st, 2020 for fever, moderate to low abundance jaundice and epistaxis (nosebleed) and painful hepatomegaly. Paraclinical examinations, such as RT-PCR, objectified yellow fever virus in post-mortem tissue sample. Thus, confirmed yellow fever cases in this district, the low level of vaccination coverage, the circulation of the virus and the presence of vector in the country should warn of a real threat of reemergence of yellow fever in Chad.

Given the significant impact of mosquito-borne flaviviruses (MBFVs) on both human and animal health, predicting their dynamics and understanding their transmission cycle is of the utmost importance. Usually, predictions about the distribution of priority pathogens, such as Dengue, Yellow fever, West Nile Virus and St. Louis encephalitis, relate abiotic elements to simple biotic components, such as a single causal agent. Furthermore, focusing on single pathogens neglects the possibility of interactions and the existence of common elements in the transmission cycles of multiple pathogens. A necessary, but not sufficient, condition that a mosquito be a vector of a MBFV is that it co-occurs with hosts of the pathogen. We therefore use a recently developed modeling framework, based on co-occurrence data, to infer potential biotic interactions between those mosquito and mammal species which have previously been identified as vectors or confirmed positives of at least one of the considered MBFVs. We thus create models for predicting the relative importance of mosquito species as potential vectors for each pathogen, and also for all pathogens together, using the known vectors to validate the models. We infer that various mosquito species are likely to be significant vectors, even though they have not currently been identified as such, and are likely to harbor multiple pathogens, again validating the predictions with known results. Besides the above \"niche-based\" viewpoint we also consider an assemblage-based analysis, wherein we use a community-identification algorithm to identify those mosquito and/or mammal species that form assemblages by dint of their significant degree of co-occurrence. The most cohesive assemblage includes important primary vectors, such as A. aegypti, A. albopictus, C. quinquefasciatus, C. pipiens and mammals with abundant populations that are well-adapted to human environments, such as the white-tailed deer (Odocoileus virginianus), peccary (Tayassu pecari), opossum (Didelphis marsupialis) and bats (Artibeus lituratus and Sturnira lilium). Our results suggest that this assemblage has an important role in the transmission dynamics of this viral group viewed as a complex multi-pathogen-vector-host system. By including biotic risk factors our approach also modifies the geographical risk profiles of the spatial distribution of MBFVs in Mexico relative to a consideration of only abiotic niche variables.

Yellow fever (YF) surveillance in Brazil is focused mainly on the detection of epizootic events regarding New World non-human primates (NWNHP). We present a challenging case of a Callitrichidae (Callithrix spp) kept as a domiciliated pet that lived in the urban area of São Paulo municipality and was positive to YF virus by RT-qPCR and immunohistochemistry. After investigation, it was the first occurrence of non-autochthonous YF case of NWNHP described, with probable place of infection in the North shore of São Paulo state. This case illustrates the importance of coordinated laboratorial and field actions, and risks posed by transit of wildlife.

We report yellow fever infection in a Dutch traveler returning from Brazil. Yellow fever virus (YFV) was identified in serum and urine samples over a period of 1 month. Yellow fever virus genome sequences from the patient clustered with recent Brazilian YFV and showed with limited nucleotide changes during the resolving infection.

Background: Yellow fever outbreaks have re-emerged in Brazil during 2016-18, with mortality rates up to 30%. Although urban transmission has not been reported since 1942, the risk of re-urbanization of yellow fever is significant, as Aedes aegypti is present in most tropical and sub-tropical cities in the World and still remains the main vector of urban YFV. Although the YFV vaccine is safe and effective, it does not always reach populations at greatest risk of infection and there is an acknowledged global shortage of vaccine supply. The introgression of Wolbachia bacteria into Ae. aegypti mosquito populations is being trialed in several countries ( www.worldmosquito.org) as a biocontrol method against dengue, Zika and chikungunya. Here, we studied the ability of Wolbachia to reduce the transmission potential of Ae. aegypti mosquitoes for Yellow fever virus (YFV). Methods: Two recently isolated YFV (primate and human) were used to challenge field-derived wild-type and Wolbachia-infected ( wMel +) Ae. aegypti mosquitoes. The YFV infection status was followed for 7, 14 and 21 days post-oral feeding (dpf). The YFV transmission potential of mosquitoes was evaluated via nano-injection of saliva into uninfected mosquitoes or by inoculation in mice. Results: We found that Wolbachia was able to significantly reduce the prevalence of mosquitoes with YFV infected heads and thoraces for both viral isolates. Furthermore, analyses of mosquito saliva, through indirect injection into naïve mosquitoes or via interferon-deficient mouse model, indicated Wolbachia was associated with profound reduction in the YFV transmission potential of mosquitoes (14dpf). Conclusions: Our results suggest that Wolbachia introgression could be used as a complementary strategy for prevention of urban yellow fever transmission, along with the human vaccination program.

Yellow fever is a noncontagious disease caused by an arbovirus in the Flaviviridae family. It is an endemic disease in the tropical forests of Africa and South America, with the mosquito as a vector. Approximately half of those infected will be asymptomatic, while 15% will develop the severe/malignant form of the disease that includes renal and hepatic failure, bleeding, and neurological impairment as the principal symptoms. The lethality of the severe form reaches up to 70%. The objective of this study was to report on the case of a patient who was transferred to the hepatobiliary unit of our service due to acute liver failure due to yellow fever. He was treated with liver transplantation. The patient progressed satisfactorily, being discharged from the intensive care unit in 10 days and discharged from the hospital within 19 days after transplantation. Despite the encouraging result of our team, this has not been applied to other centers that have also performed this modality of treatment; therefore, the question remains as to whether and when to recommend liver transplantation for treatment of severe yellow fever.

Between December 2015 and July 2016, a yellow fever (YF) outbreak affected urban areas of Angola and the Democratic Republic of the Congo (DRC). We described the outbreak in DRC and assessed the accuracy of the YF case definition, to facilitate early diagnosis of cases in future urban outbreaks.
In DRC, suspected YF infection was defined as jaundice within 2 weeks after acute fever onset and was confirmed by either IgM serology or PCR for YF viral RNA. We used case investigation and hospital admission forms. Comparing clinical signs between confirmed and discarded suspected YF cases, we calculated the predictive values of each sign for confirmed YF and the diagnostic accuracy of several suspected YF case definitions. Fifty seven of 78 (73%) confirmed cases had travelled from Angola: 88% (50/57) men; median age 31 years (IQR 25-37). 15 (19%) confirmed cases were infected locally in urban settings in DRC. Median time from symptom onset to healthcare consultation was 7 days (IQR 6-9), to appearance of jaundice 8 days (IQR 7-11), to sample collection 9 days (IQR 7-14), and to hospitalization 17 days (IQR 11-26). A case definition including fever or jaundice, combined with myalgia or a negative malaria test, yielded an improved sensitivity (100%) and specificity (57%).
As jaundice appeared late, the majority of cases were diagnosed too late for supportive care and prompt vector control. In areas with known local YF transmission, a suspected case definition without jaundice as essential criterion could facilitate earlier YF diagnosis, care and control.