This study describes a case series of nine cases with YF in the GS from 1990 to 2022. Most of the cases were described in FG: one from Suriname (traveler), two from Venezuela, and one from Amapá (Brazil). No cases have been reported in Guyana, and no autochthonous case in Suriname.

With a 78% case-fatality rate, the results of the present study differ significantly from other results in the literature in South America [14, 15]. Indeed, pre-existing studies mentioned a case-fatality rate of 20% in Africa and 33% during the Brazilian epidemic [4, 16]. However, the small number of patients included in this study and the severity of their clinical state on arrival may affect the relevance of the result obtained. Moreover, there is no systematic biological research of YF against any undocumented infectious disease case, so the real incidence may be underestimated, mainly in FG wedged between countries that have recently experienced epidemics.

In this case series, almost half of the patients had a co-infection with another pathogen. This differs sensibly from what is described in the literature [17]. Co-infection with yellow fever is rare, but has been described in the literature. Dengue serotype 2 an YF co-infection was reported during the YF outbreak in Brazil [6]. In Angola, a study reported a co-infection between Japanese encephalitis and YF [18]. In the Kedougou region, Senegal, seven cases of P. falciparum and YF co-infection were reported [19]. Arbovirus and malaria co-infections have already been described, but more often with dengue [20]. A case of West Nile virus co-infection has also been described in evidence of arbovirus co-infection in patients with malaria and typhoid fever in Nigeria [21]. All these pathologies are transmitted by mosquitoes and the same mosquito carries different viruses/parasites. Thus, the Brazilian Aedes aegypti is a competent vector for multiple complex arboviral co-infections [22]. Moreover, it is also possible that in these regions where mosquitoes are numerous, co-infection is the result of the bite of several mosquitoes, each being vector of one disease.

Another hypothesis is YF may work by altering immune defense systems and facilitating co-infections. This has already been described with measles: measles pneumonitis is frequently a source of bacterial and viral co-infection [23, 24]. A third hypothesis may also be that serological diagnostic methods lack specificity. It has been described in March 2019 a 20-year-old Peruvian young man positive by RT-PCR for YF in Condorcanqui, Department of Amazonas. He also had a positive microscopic agglutination test for leptospirosis. Discussion does not allow to decide between false positive and real co-infection [25].

There are three types of YF transmission cycles. The first is a wild and sylvatic cycle where NHP are the primary reservoir with occasional transmission to humans. The second cycle is semi-domestic, at the forest edge, where mosquitoes infect both monkeys and people [26]. The last cycle is urban, when infected people introduce the virus into densely populated areas with high mosquito density and where people have little immunity. In these conditions, infected mosquitoes transmit the virus from person to person and may be responsible for epidemics such as recently occurred in Brazil.

Currently, only the wild cycle exists in FG and is vectored by Haemagogus and Sabethes mosquitoes [27, 28]. The high vaccination coverage rate and the low population density in these areas undoubtedly contribute to epidemic risk control. However, semi-domestic and urban areas harbor A. aegypti, which may be an effective vector of YF. The latter is already responsible for dengue epidemics, the emergence of chikungunya virus in 2013 and Zika virus in 2016, in the GS. Moreover, A. aegypti represents a potential vector of YF which could thus spread in cities [29]. The animal reservoir of YF also plays an important role in the risk of spread: it relies mainly on NHP, but it is important to note that the virus has been documented in many tropical species [28, 29]. Thus, although there are no recent studies performed on YF virus circulation in primates in the GS, it has previously been strongly associated with infection of red howler monkeys (Alouatta seniculus) [28]. Monkeys are particularly susceptible to the disease and act as a reservoir [3]. Nevertheless, even though the virus is currently circulating in forest habitats, anthropogenic activities increase the risk of transmission. Deforestation, especially for agriculture and cattle grazing, is associated with the emergence of YF outbreaks [27]. Host density is also a crucial factor of transmission rates. These environmental changes, such as immigration and economic development responsible for increased population density, may create new foci of transmission or new sources of zoonotic infections [27]. Finally, during the global COVID-19 pandemic, many preventive programs, such as YF vaccination, have been delayed for several months. This disruption may participate in increasing the risk of YF emergence [30, 31].

One track for the future would be the use of mosquitoes infected with Wolbachia, as in the article by Utarini et al. By infecting Ae. aegypti in Indonesia, they showed a decline significant dengue-related infections and a decrease in hospitalizations [32].

In this case series, two patients were vaccinated, three were not vaccinated, and four had an undetermined status. In FG, where most cases were recorded, YF vaccination coverage was estimated at 95% (95% CI = 93.4–96.2) [33]. This result was heterogeneous, with the lowest levels near the border with Suriname [34, 35]. Moreover, the two vaccinated patients did not have IgG, reflecting a lack of vaccine immunity. The first patient got YF 13 years after vaccination, which was attributed to a poor antibody response, or an inadequate vaccine storage, breaking the thermostability chain, or a deficient immune system. The second patient received the vaccine before her second birthday, but never received the recommended booster.

In 2013, WHO advocated that a single dose of vaccine was sufficient for life, whereas vaccination was reviewed every previous decade [36]. Justification for the absence of booster dose in endemic areas is that immunity may be naturally boosted as a result of exposure to the wild-type virus. Nevertheless, data from the 2016 Brazilian epidemic do not support this theory, where 3.24% (27/832) of YF patients had already received vaccination less than 10 years earlier, and 52% (432/832) had been vaccinated more than 10 years earlier [37, 38]. Amanna and Slifka’s findings argue for a loss of immunization: antiviral immunization might be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination. Early vaccination during childhood may be an increased risk for failure [39]. Thus, the booster dose, although outside the recommendations, remains controversial in immunocompromised individuals or immunocompetent subjects traveling 10 years after their first doses in endemic areas [40, 41].

The Brazilian Ministry of Health has chosen to maintain two doses of YF vaccine in the national calendar, whereas the French health authorities adopted, according to the Strategic Advisory Group of Experts on Immunization and the amendments of the International Health Regulations in February 2016, the use of a single dose of vaccine for residents and travelers [27]. This is even more relevant given the shortage of YF vaccines during the 2016 epidemic, where Brazilians were vaccinated with doses corresponding to 1/5 of the dose usually used, to allow sufficient vaccination coverage. More generally, there is no common YF vaccination strategy in the GS.

About the limitations of this study, only one hospital reviewed case histories. We can also add that it relied only on published cases, and even had to look for experts. The nature of the study does not allow estimating mortality or morbidity of the disease in GS, because only the serious cases are published. Finally, we can affirm we have a problem of epidemiological surveillance for yellow fever.