Epidemiology of West Nile virus in Africa: an underestimated threat

12openInternationalInternational coauthor/editorBackground West Nile virus is a mosquito-borne flavivirus which has been posing continuous challenges to public health worldwide due to the identification of new lineages and clades and its ability to invade and establish in an increasing number of countries. Its current distribution, genetic variability, ecology, and epidemiological pattern in the African continent are only partially known despite the general consensus on the urgency to obtain such information for quantifying the actual disease burden in Africa other than to predict future threats at global scale. Methodology and principal findings References were searched in PubMed and Google Scholar electronic databases on January 21, 2020, using selected keywords, without language and date restriction. Additional manual searches of reference list were carried out. Further references have been later added accordingly to experts’ opinion. We included 153 scientific papers published between 1940 and 2021. This review highlights: (i) the co-circulation of WNV-lineages 1, 2, and 8 in the African continent; (ii) the presence of diverse WNV competent vectors in Africa, mainly belonging to the Culex genus; (iii) the lack of vector competence studies for several other mosquito species found naturally infected with WNV in Africa; (iv) the need of more competence studies to be addressed on ticks; (iv) evidence of circulation of WNV among humans, animals and vectors in at least 28 Countries; (v) the lack of knowledge on the epidemiological situation of WNV for 19 Countries and (vii) the importance of carrying out specific serological surveys in order to avoid possible bias on WNV circulation in Africa. Conclusions This study provides the state of art on WNV investigation carried out in Africa, highlighting several knowledge gaps regarding i) the current WNV distribution and genetic diversity, ii) its ecology and transmission chains including the role of different arthropods and vertebrate species as competent reservoirs, and iii) the real disease burden for humans and animals. This review highlights the needs for further research and coordinated surveillance efforts on WNV in Africa.openMencattelli, G.; Dior Ndione M.H.; Rosa', R.; Marini, G.; Diagne, C.T.; Diagne, M.M.; Fall, G.; Faye, O.; Diallo, M.; Faye, O.; Savini, G.; Rizzoli, A.Mencattelli, G.; Dior Ndione, M.H.; Rosa', R.; Marini, G.; Diagne, C.T.; Diagne, M.M.; Fall, G.; Faye, O.; Diallo, M.; Faye, O.; Savini, G.; Rizzoli, A

Impact of genetic diversity on biological characteristics of Usutu virus strains in Africa

Usutu virus (USUV) previously restricted to Africa where it caused mild infections, emerged in 2001 in Europe and caused more severe infections among birds and humans with neurological forms, suggesting an adaptation and increasing virulence. This evolution suggests the need to better understand USUV transmission patterns for assessing risks and to develop control strategies. Phylogenetic analysis conducted in Africa showed low genetic diversity of African USUV strains except for one human and the USUV subtype (USUVsub) strains, which exhibited a deletion in the 3′UTR and nucleotide substitutions throughout the genome. Here we analyzed their viral replication in vitro in mosquito and mammalian cells, and vector competence of Culex quinquefasciatus, compared to a reference strain. Growth kinetics of the different strains showed comparable replication rates however variations in replication and translation efficiency were observed. Vector competence analysis showed that all strains were able to infect Culex quinquefasciatus the main peridomestic Culex species in Africa, with detection of USUV viral genomes and infectious particles. Dissemination and transmission were observed only for USUVsub, but infectious particles were not detected in Culex quinquefasciatus saliva. Our findings suggest that genetic variability can affect USUV in vitro replication in a cell type-dependent manner and in vivo in mosquitoes. In addition, the results show that Culex quinquefasciatus is not competent for the USUV strains analyzed here and also suggest an aborted transmission process for the USUVsub, which requires further investigations

Spatial and temporal dynamics of West Nile virus between Africa and Europe

It is unclear whether West Nile virus (WNV) circulates between Africa and Europe, despite numerous studies supporting an African origin and high transmission in Europe. We integrated genomic data with geographic observations and phylogenetic and phylogeographic inferences to uncover the spatial and temporal viral dynamics of WNV between these two continents. We focused our analysis towards WNV lineages 1 (L1) and 2 (L2), the most spatially widespread and pathogenic WNV lineages. Our study shows a Northern-Western African origin of L1, with back-and-forth exchanges between West Africa and Southern-Western Europe; and a Southern African origin of L2, with one main introduction from South Africa to Europe, and no back introductions observed. We also noticed a potential overlap between L1 and L2 Eastern and Western phylogeography and two Afro-Palearctic bird migratory flyways. Future studies linking avian and mosquito species susceptibility, migratory connectivity patterns, and phylogeographic inference are suggested to elucidate the dynamics of emerging viruse

Usutu Virus Isolated from Rodents in Senegal

Usutu virus (USUV) is a Culex-associated mosquito-borne flavivirus of the Flaviviridae family. Since its discovery in 1959, the virus has been isolated from birds, arthropods and humans in Europe and Africa. An increasing number of Usutu virus infections in humans with neurological presentations have been reported. Recently, the virus has been detected in bats and horses, which deviates from the currently proposed enzootic cycle of USUV involving several different avian and mosquito species. Despite this increasing number of viral detections in different mammalian hosts, the existence of a non-avian reservoir remains unresolved. In Kedougou, a tropical region in the southeast corner of Senegal, Usutu virus was detected, isolated and sequenced from five asymptomatic small mammals: Two different rodent species and a single species of shrew. Additional molecular characterization and in vivo growth dynamics showed that these rodents/shrew-derived viruses are closely related to the reference strain (accession number: AF013412) and are as pathogenic as other characterized strains associated with neurological invasions in human. This is the first evidence of Usutu virus isolation from rodents or shrews. Our findings emphasize the need to consider a closer monitoring of terrestrial small mammals in future active surveillance, public health, and epidemiological efforts in response to USUV in both Africa and Europe

Vector competence of anthropophilic mosquitoes for a new mesonivirus in Senegal

International audienceThe mesoniviruses (MESOVs) belong to the newly described Mesoniviridae family (Order: Nidovirales). They have never been reported in Senegal until recently during a study in arbovirus emergence with the detection of a new species of MESOV named Dianke virus (DKV) from common mosquitoes from eastern Senegal. Actually, their vector competence for this newly described DKV is unknown. We, therefore, estimated the vector competence of Culex tritaeniorhynchus, Culex quinquefasciatus, Aedes aegypti, and Anopheles gambiae mosquitoes collected in Senegal for DKV using oral infection. Whole bodies, legs/wings, and saliva samples were tested for DKV by RT-PCR to estimate infection, dissemination, and transmission rates. The infectivity of virus particles in the saliva was confirmed by infecting C6/36 cells. Virus transmission rates were up to 95.45% in Culex tritaeniorhynchus, 28% in Cx. quinquefasciatus and 9.09% in Aedes aegypti. Viral particles in the saliva were confirmed infectious by C6/36 cell culture. An. gambiae was able to disseminate DKV only at 20 days post-infection. This study shows that Culex mosquitoes are more competent than Ae. aegypti for DKV, while Anopheles gambiae is not likely a competent vector

First Detection of the West Nile Virus Koutango Lineage in Sandflies in Niger

West Nile virus (WNV), belonging to the Flaviviridae family, causes a mosquito-borne disease and shows great genetic diversity, with at least eight different lineages. The Koutango lineage of WNV (WN-KOUTV), mostly associated with ticks and rodents in the wild, is exclusively present in Africa and shows evidence of infection in humans and high virulence in mice. In 2016, in a context of Rift Valley fever (RVF) outbreak in Niger, mosquitoes, biting midges and sandflies were collected for arbovirus isolation using cell culture, immunofluorescence and RT-PCR assays. Whole genome sequencing and in vivo replication studies using mice were later conducted on positive samples. The WN-KOUTV strain was detected in a sandfly pool. The sequence analyses and replication studies confirmed that this strain belonged to the WN-KOUTV lineage and caused 100% mortality of mice. Further studies should be done to assess what genetic traits of WN-KOUTV influence this very high virulence in mice. In addition, given the risk of WN-KOUTV to infect humans, the possibility of multiple vectors as well as birds as reservoirs of WNV, to spread the virus beyond Africa, and the increasing threats of flavivirus infections in the world, it is important to understand the potential of WN-KOUTV to emerge

Re-Emergence of Dengue Serotype 3 in the Context of a Large Religious Gathering Event in Touba, Senegal

Dengue virus (DENV) was detected in Senegal in 1979 for the first time. Since 2017, unprecedented frequent outbreaks of DENV were noticed yearly. In this context, epidemiological and molecular evolution data are paramount to decipher the virus diffusion route. In the current study, we focused on a dengue outbreak which occurred in Senegal in 2018 in the context of a large religious gathering with 263 confirmed DENV cases out of 832 collected samples, including 25 life-threatening cases and 2 deaths. It was characterized by a co-circulation of dengue serotypes 1 and 3. Phylogenetic analysis based on the E gene revealed that the main detected serotype in Touba was DENV-3 and belonged to Genotype III. Bayesian phylogeographic analysis was performed and suggested one viral introduction around 2017.07 (95% HPD = 2016.61–2017.57) followed by cryptic circulation before the identification of the first case on 1 October 2018. DENV-3 strains are phylogenetically related, with strong phylogenetic links between strains retrieved from Burkina Faso and other West African countries. These phylogenetic data substantiate epidemiological data of the origin of DENV-3 and its spread between African countries and subsequent diffusion after religious mass events. The study also highlighted the usefulness of a mobile laboratory during the outbreak response, allowing rapid diagnosis and resulting in improved patient management

Reemergence of Sylvatic Dengue Virus Serotype 2 in Kedougou, Senegal, 2020

In 2020, a sylvatic dengue virus serotype 2 infection outbreak resulted in 59 confirmed dengue cases in Kedougou, Senegal, suggesting those strains might not require adaptation to reemerge into urban transmission cycles. Large-scale genomic surveillance and updated molecular diagnostic tools are needed to effectively prevent dengue virus infections in Senegal

Re-Emergence of Rift Valley Fever Virus Lineage H in Senegal in 2022: In Vitro Characterization and Impact on Its Global Emergence in West Africa

Rift Valley fever (RVF) is a re-emerging vector-borne zoonosis with a high public health and veterinary impact. In West Africa, many lineages were previously detected, but since 2020, lineage H from South Africa has been the main cause of the outbreaks. In this study, clinical samples collected through national surveillance were screened for RVF virus (RVFV) acute infection by RT-PCR and IgM ELISA tests. Sequencing, genome mapping and in vitro phenotypic characterization in mammal cells were performed on RT-PCR positive samples in comparison with other epidemic lineages (G and C). Four RVFV human cases were detected in Senegal and the sequence analyses revealed that the strains belonged to lineage H. The in vitro kinetics and genome mapping showed different replication efficiency profiles for the tested RVFV lineages and non-conservative mutations, which were more common to lineage G or specific to lineage H. Our findings showed the re-emergence of lineage H in Senegal in 2022, its high viral replication efficiency in vitro and support the findings that genetic diversity affects viral replication. This study gives new insights into the biological properties of lineage H and calls for deeper studies to better assess its potential to cause a future threat in Senegal

Novel Amplicon-Based Sequencing Approach to West Nile Virus

West Nile virus is a re-emerging arbovirus whose impact on public health is increasingly important as more and more epidemics and epizootics occur, particularly in America and Europe, with evidence of active circulation in Africa. Because birds constitute the main reservoirs, migratory movements allow the diffusion of various lineages in the world. It is therefore crucial to properly control the dispersion of these lineages, especially because some have a greater health impact on public health than others. This work describes the development and validation of a novel whole-genome amplicon-based sequencing approach to West Nile virus. This study was carried out on different strains from lineage 1 and 2 from Senegal and Italy. The presented protocol/approach showed good coverage using samples derived from several vertebrate hosts and may be valuable for West Nile genomic surveillance