key: cord-0288832-jqjy1pdx authors: Lehmann, Tovi; Kouam, Cedric; Woo, Joshua; Diallo, Mawlouth; Wilkerson, Richard; Linton, Yvonne-Marie title: The African mosquito-borne diseasosome: Geographical patterns and range expansion date: 2021-12-23 journal: bioRxiv DOI: 10.1101/2021.12.21.473756 sha: 2a91a23a3c07b61c06e68766b398aa4a178a5f61 doc_id: 288832 cord_uid: jqjy1pdx Mosquito-borne diseases (MBDs) such as malaria, dengue, and Rift Valley fever threaten public health and food security globally. Despite their cohesive nature, they are typically treated as distinct entities. Applying biological system analysis to the African MBDs from a One Health perspective, we provide the first biogeographic description of the African mosquito fauna corresponding with the pathogens they transmit. After compiling records accumulated over a century, we find that there are 677 mosquito species in Africa, representing 16 genera, and 151 mosquito-borne pathogens (MBPs) circulating primarily among wild tetrapods, dominated by viruses (95) and protozoans (47). We estimate that reported MBPs represent ∼1% of the actual number. Unlike mosquitoes, African arboviruses and mammalian plasmodia represent a higher share of the World’s total based on the area – species richness relationship (P<0.0001), explaining the disproportional large share of global MBPs that originated from Africa. Species richness of African mosquitoes and MBPs are similarly concentrated along the equator, peaking in central Africa, with a secondary “ridge” along eastern Africa. Moderate diversity and low endemicity in mosquitoes across the Sahel reveals a fauna with high propensity for long-range migration. Regional differences in species richness, endemicity, and composition agreed with country-based results. The composition of mosquitoes and MBPs separates sub-Saharan Africa from north Africa, in accordance with the Palearctic and Afrotropical faunal realms, and west and central Africa are clustered together distinctly from the cluster of eastern and southern Africa. With ∼25% of the species occupying a single country, ∼50% in 1–3 countries and <5% found in >25 countries, the typical ranges of both mosquitoes and MBPs are surprisingly small. The striking similarity in diversity and especially in range distributions of mosquitoes and MBPs suggest that most MBPs are transmitted by one or few narrow-range mosquito vectors. Exceptionally widespread mosquito species (e.g., Ae. aegypti, Cx. quinquefasciatus, and 10 Anopheles species) feed preferentially on people and domestic animals, and nearly half are windborne migrants. Likewise, exceptionally widespread MBPs are transmitted between people or domestic animals and are vectored by one or more of the aforementioned widespread mosquitoes. Our results suggest that few MBPs have undergone a dramatic range expansion, after adapting to people or domestic animals as well as to exceptionally-widespread mosquitoes. During the intermediate phase of range expansion, MBPs extend their vector and vertebrate host ranges with a concomitant gradual increase in geographical range. Because range size may serve as a marker of the phase of range expansion, ranking the African MBPs according to range, we identified several MBPs that pose elevated risk for disease emergence (e.g., Wesselsbron virus). Taken together, our database, approach, and results can help improve MBD surveillance and lead to a better understanding of disease emergence. This knowledge has the potential to improve capacity to prevent and mitigate new and emerging MBD threats. Africa carries the heaviest global burden of mosquito borne diseases (MBDs), with more than 51 400,000 deaths attributable to malaria of the 700,000 caused by vector-borne diseases annually 52 (WHO, 2020). At least eight of the 11 topmost impactful global mosquito-borne pathogens 53 (MBPs) originated in Africa-namely Yellow Fever virus (YFV), West Nile virus (WNV), 54 Chikungunya virus (CHIKV), Rift Valley fever virus (RVFV), Zika virus (ZIKV) and three human 55 Plasmodium species (falciparum, malariae, ovale) (WHO, 2020). Excluding its islands, Africa 56 comprises only 20% of the earth's land surface, but is the origin of 73% (8 of 11) of these global 57 MBPs. Based on the species richness -area relationship (Lomolino, 2020) , this excess is highly 58 significant (P<0.001, exact binomial test), corroborating a recent literature review that has 59 reached a similar conclusion using different data (Swei et al., 2020) . The reasons for Africa's 60 disproportional role as the origin of so many global MBPs may include being the only continent 61 that extends from the northern to southern temperate zones, covering >70 ○ of latitudes (37 ○ N-62 34 ○ S), and straddling several biomes including the outstandingly diverse equatorial forest 63 (Burgess et al., 2004; Guernier et al., 2004; Lomolino, 2020) . As the homeland of the hominids 64 and extant apes, we expected that Africa would contain most human MBPs (Wolfe et al., 2007) , 65 yet, five of the eight global MBDs are zoonotic (YF, WN, RVF, CHIK, and ZIK), leading to a new 66 hypothesis that Africa has more MBDs in total, not only those affecting humans. Africa is also 67 home to the largest number of megafauna species, and thus it poses a greater risk to many 68 phylogenetically related domestic animals. Understanding the MBDs of Africa, therefore, would 69 be valuable for global health and food security. As Africa undergoes dramatic perturbations due 70 to deforestation and global climate change (e.g., desertification), coupled with food and water 71 scarcity, the risk for the emergence/re-emergence of MBDs should be closely monitored. 72 Baseline knowledge is a prerequisite to successful mitigation of MBDs, however-as we have 73 found-this vital information is scarce and not readily accessible. 74 The study of MBDs has traditionally been fragmented into separate fields: virology, parasitology, 75 entomology, etc. Most studies have focused on one or a few related pathogens, and/or their 76 vectors in a limited region. Excepting a few reviews of certain MBDs (Weaver et al., 2012; 77 Braack et al., 2018) , the ensemble of MBDs as a biological system composed of mosquitoes 78 and pathogens has never before been holistically studied to our knowledge. On the other hand, 79 the increasing frequency of disease emergence in humans has deservedly been the focus of 80 extensive study (Burke, 1998 Here, focusing on the MBDs in continental Africa from a One Health perspective, we include all 84 known pathogens transmitted by mosquitoes to terrestrial tetrapods, and compare 85 biogeographical features of this disease system after constructing a dedicated database, based 86 on a comprehensive literature search (Supp. Materials). We describe the composition and 87 geographical organization of the mosquito species and the MBPs in Africa to better understand 88 the process of MBD range expansion. Specifically, we evaluate the hypothesis that Africa has 89 exceptionally high mosquito and MBP diversities, and map the landscapes of their species 90 richness, endemicity, and composition. The results lead to insights into the role of mosquito and 91 MBP dispersal, the nature of barriers to their spread, and the future of MBD surveillance in 92 Africa. Evaluating variation in range size of mosquito and MBP species and attributes of 93 extremely widespread species, we propose a process for range expansion of MBDs and 94 accordingly rank the African MBDs as to their present phase of range expansion as a marker of 95 risk for disease emergence. 96 Despite being studied for over a century, the main vector species of MBPs of vertebrates remain 97 largely unknown, including many sylvatic vectors (transmitting among wild animals) of the most 98 well-studied pathogens (Karabatsos, 1985 Weaver et al., 2020; Wilkerson et al., 2021) . This is also the case for many MBP species of 101 vertebrates (Karabatsos, 1985; Njabo et al., 2009; Weaver et al., 2012; Perkins, 2014 Perkins, , 2018 . 102 Therefore, it is most likely that the role of many mosquito species as vectors of known and 103 unknown pathogens is yet to be discovered. Accordingly, we included all known African 104 mosquitoes as the basis for describing and understanding patterns that we expect would also 105 apply to as yet unrecognized mosquito vector species. In this exploratory analysis, we 106 summarize trends based on knowledge that has been accumulated over at least 120 years. 107 With the expected growth in this domain due to the renewed recognition of the value of disease 108 surveillance brought about by the ongoing COVID-19 pandemic, as well as the advance in 109 methodologies such as metagenomics, it would be valuable to revisit these trends every decade 110 and assess the changes in the patterns described herein. 111 As many of the records on mosquito and MBP distribution were collected before 1980, reliable 113 localization of a large portion of these records is only available at the country level (Karabatsos, 114 1985 classes (Linder et al., 2012) , and vary in size, our analysis addresses fuzzy eco-geographic 118 units. 119 Composition of African mosquitoes and mosquito-borne pathogens 120 Continental Africa, which comprises 20% of the Worlds land surface, supports 19% of all known 121 global mosquito species (N = 3,570, see Methods) (Wilkerson et al., 2021) . The African 122 mosquito fauna is represented by 677 species spanning 16 genera and 53 subgenera, with 123 Aedes comprising the largest number of species, followed by Anopheles and Culex (Fig. 1a) . Goodness of fit tests of 20% across the 16 represented genera where N >15 species/genus 125 revealed higher fractions of African species in Aedes (23%, P<0.01, X 2 1=6.9), in Anopheles 126 (30%, P<0.0001, X 2 1 = 27.5), and in Coquillettidia (40%, P<0.0002, X 2 1=14.0), but was 127 insignificant in the other genera. The highest fraction of African species (100%) is found in the 128 genus Eretmapodites (n = 48), which is endemic to Africa (Fig. 1a) . Fractions >20% were found 129 in several genera, indicating local speciation on the continent. Among the 53 mosquito 130 subgenera in Africa, Anopheles subgenus Cellia is by far the most speciose (n = 121, Fig. 1b, 131 Table S1). Several subgenera have a high proportion of African species (Fig. 1b) , although most 132 of these have a small number of species in total, e.g., Anopheles subgenus Christya (n= 2). 133 Nonetheless, the 29 Aedes species in the subgenus Catageiomyia are exclusively African 134 species and 24 of the 28 species of the Aedes subgenus Neomelaniconion are African (Fig. 1b , 135 Table S1 ). While not precluding that some of the species also occur outside Africa, a high 136 fraction of species found in Africa, especially in taxa with large number of species, highlights the 137 fauna's unique elements. 138 A total of 151 known mosquito-borne-pathogen species (MBPs) affecting vertebrates have been 139 reported from continental Africa (Fig. 1c) . These include 95 viruses, 47 protozoans, six 140 helminths, and three bacteria, comprising a total of 16 families and 30 genera (Fig. 1c, including 141 3 unclassified genera). These 95 arboviruses represent a significantly higher share than 142 expected from the known global total based on the surface land area of Africa (32% vs. 20%, 143 P<0.0001, X 2 1=25.5). The fraction of MB arboviruses is likely even higher because among the 144 total of 300 arboviruses that have been isolated from mosquito pools worldwide ( birds were not considered here because recent molecular analyses revealed many lineages that 149 likely represent yet-to-be named species (Bensch et al., 2009; Njabo et al., 2009; Perkins, 150 2014). Additionally, many trans-continental migrant birds may be exposed to plasmodia only in 151 Europe and Asia (Hellgren et al., 2007) and thus should not be considered African -a problem 152 that may apply to other avian pathogens. 153 The vast majority of MBPs are maintained in wild hosts reservoirs (Fig. 1d) , although a few can 169 be transmitted for short periods between humans, e.g., YFV, O'nyong'nyong virus (ONNV) or 170 domestic animals e.g., RVFV. Mosquito transmission is the primary route of vertebrate infection 171 in the majority of the MBPs (Fig. 1c) , whereas 16 pathogens rely on other arthropods or on 172 direct transmission as their primary mode of transmission and use mosquitoes as a secondary 173 route (Fig 1c) . At least 8 of the 9 poxviruses are transmitted mechanically by mosquitoes as are 174 the three bacteria (Turell & Knudson, 1987) (Fig.1c , Supp. File 2). Mechanical transmission 175 appears to be linked to secondary transmission (Fig. 1c , Supp. File 2), although certain 176 poxviruses can be transmitted several weeks post exposure (Kligler et al., 1928; DaMassa, 177 1966) . 178 Crude range approximations defined by the number of African countries occupied by mosquito 180 species revealed that 26% of all African mosquito species are endemic (known only within a 181 single country), and that over 50% are restricted to only 1-3 countries (median= 3.0, Fig. 2a ). 182 The L-shape distribution reveals that only 5% of the total number of species are widespread 183 across over half the continent (i.e., occupying 26 or more countries, Fig. 2a and blood-feed on people or domestic animals (Fig. 2a) , whereas at least six engage in high 207 altitudes wind-borne migration based on recent studies in Mali (Huestis et al., 2019) . 208 The distribution of African MBPs is remarkably similar to that of the mosquitoes (Fig. 2b) , with 209 28% being single country-endemic, 56% found in 1-3 countries (median= 3.0), and 5% found in 210 26 or more countries (i.e., over approximately half the continent). The Pearson correlation 211 coefficient between the number of countries and total area occupied by each MBP species is 212 0.967 (N= 151, P<0.0001), corroborating the suitability of the number of countries as an index of 213 total area. The median area occupied by a MBP is 2.15 x10 6 km 2 (95% CI: 1.64-2.65 x10 6 km 2 ). 214 The most widespread MBPs (40 countries) are Pl. falciparum and Pl. vivax (PLFLC, PLVIX) with 215 only nine MBPs being reported in 20 or more countries (Fig. 2b) . Except West Nile virus (WNV), 216 which is primarily transmitted among birds (including migratory birds), all of these exceptionally 217 widespread MBPs are transmitted among humans (6) or domestic animals (2), and without 218 exception, all are vectored by at least one of the most widespread mosquito species mentioned 219 above (Fig. 2a According to the area -species richness principle (Lomolino, 2020) , mosquito species richness 227 has been found to increase with a country's area in a worldwide analysis (Foley et al., 2007) . In 228 Africa, this relationship accounted for only 13% of the variance compared to 42% worldwide, 229 highlighting the importance of other factors (Fig. 3a) . The regions of highest species richness 230 include a belt along the equatorial forest, which appears widest in central Africa (Fig. 3a) . The 231 countries with highest species richness include DRC, Cameroon, Uganda, Kenya, Nigeria, and 232 Ivory Coast. Adjusting for area minimally changes these countries' ranking ( Fig. 3a) . North Africa 233 represents a uniform belt of lowest mosquito diversity (Figs. 3a) with Libya being an extreme 234 outlier that exceeds the 95% CL, given its area (Fig. 3a) . A corridor of modest diversity along 235 the Sahel (from Mauritania to Chad), and possibly another corridor between central and East 236 Africa includes countries from Namibia and Botswana to Rwanda, which remains stable after 237 accommodating country area (Fig. 3a) . 238 Similar to mosquitoes, species richness of African MBPs is highest in Central Africa, followed by 239 an East African zone stretching from Kenya to South Africa (Fig. 3b) . Except Senegal and the 240 Ivory Coast, West Africa exhibits lower diversity of MBPs than East Africa. Sahelian countries 241 and those between Central and East Africa exhibit lower MBP richness than the surrounding 242 regions, whereas North Africa exhibits the lowest MBP richness (Fig. 3b ). Species richness 243 increased with country's size, but this relationship accounted for only 13% of the variance 244 among countries (excluding outliers: Libya, increased R 2 to 23%, Fig. 3b ). 245 The distribution of country endemic mosquito species reveals greater heterogeneity than 246 species richness, with highest endemicity in Equatorial Central Africa, especially Cameroon 247 (31), followed by South Africa and Angola (22, Fig. 4a ). These three countries represent outliers 248 after accommodating species richness and, indirectly, country area (captured by species 249 richness, Fig. 3a ). Unlike species richness, lowest mosquito endemicity is found across the 250 Sahel from Mauritania to Somalia and, notably, extending to equatorial West Africa. Additionally, 251 the secondary "corridor" of low species richness separating South Africa from Central and East 252 Africa (Fig. 3a) appears wider for endemicity. Countries without known endemic mosquito 253 species included Chad and Mozambique (Fig. 4a) . The number of endemic species per country 254 is correlated with the total species richness (r= 0.7, N= 45, P< 0.001, Fig. 4a ), but the 255 relationship was not monotonic, and visual inspection suggests a higher slope after species 256 richness exceeds ~100 species per country (Figs. 3a and 4a). 257 Country-endemic MBPs comprised 25 arboviruses, 11 plasmodia, and 1 nematode, reflecting 265 similar proportion of endemicity across taxa: 27.5%, 25.6%, and 16.7%, respectively. Endemic 266 MBPs showed an extreme hotspot in Central African Republic, moderate endemism in Ivory 267 coast, followed by Nigeria and Cameroon, Egypt, and Morocco ( Fig. 4b) . Endemic MBP species 268 per country also increased with species richness and indirectly with species area, which was a 269 determinant of the latter (Fig. 3b ). After accounting for species richness, the Central African 270 Republic remains an outlier endemic hotspot, towering over all other countries. 271 Heterogeneity in species composition across regional and country scales 280 Because countries differ considerably in surveillance effort, a regional analysis, whereby each 281 region consists of multiple countries, exhibits less variability in surveillance effort and can be 282 used to ascertain the patterns noted at the country level. Five regions were defined to group 283 neighboring countries together and maximize distances among regions, accommodate 284 latitudinal variation, and minimize inter-region enclaves (without regard to political regions, 285 specific ecological, or species distributional data, Methods). Over 40% of the mosquito species 286 are region-endemic and 60% of the mosquito species are found in 1-2 regions. Only 19% are 287 found across sub-Saharan Africa and merely 3% are distributed across the five regions ( Fig. 5a : 288 histogram). Consistent with country results (Fig. 4a) , the highest mosquito richness and 289 endemicity are found in Central Africa and the lowest species richness is in North Africa. 290 Notably, endemicity is lowest in West Africa (Fig. 5a ). Significant excesses of species richness 291 based on the region size were found in West and Central Africa, whereas a significant deficit 292 was found in North Africa (P<0.01, Z> 3.1, Exact Binomial tests, Fig. 6a ). Significant excess of 293 endemic species was detected in Central Africa, whereas West Africa exhibits the lowest 294 endemicity and largest deficit of endemic species based on its size, reflecting the large number 295 of species it shares with Central Africa (N= 57), as well as with both East and Central Africa (N= 296 60, Fig. 5a ). 297 Similar to trends seen for mosquitoes, 38% of the MBP species are region-endemic, 60% are 298 found in 1-2 regions, only 10% are found across sub-Saharan Africa, and an additional 11% are 299 found across the continent ( Fig. 5b: MBPs are found in West, North, and East Africa in accord with expectations based on area ( Fig. 307 5b, P>0.05). West and Central Africa share more MBPs than other region pairs, whereas North 308 Africa shares the fewest MBPs with all adjoining regions (Fig. 5b) . Overlapping MBPs between 309 three regions was especially high between West, Central, and East Africa (N= 16) compared to 310 other combinations (1-4, Fig. 5 ). 311 The regional mosquito fauna is split into sub-Sahara and North Africa -the most distinct 321 divisions in term of mosquito species composition, followed by further split of sub-Saharan 322 Africa between the West -Central and the East -Southern fauna ( Fig. 6a: top) . A country-based 323 dendrogram reveals a more complex picture ( Fig. 6a : bottom). Most countries from West and 324 Central Africa are grouped together, as are countries from East and Southern Africa (Fig. 6a ). Nine of the twelve high similarity clusters (R 2 >0.9) group countries from the same region, with 326 only three exceptions (Nigeria-Ghana, Ivory Coast-Central African Republic, and DRC-327 Uganda, Fig. 6a ), which share ecological similarity if not geographic continuity. The country 328 dendrogram suggests substantive differences in mosquito faunas between Sahelian and 329 equatorial West Africa countries, which is further supported by the grouping of Chad with Niger, 330 as well as Nigeria with Liberia. Assemblages of mosquitoes defined by their significant co-331 occurrence in particular areas, independently from the regions defined above are illustrated in 332 The composition of the MBPs at the regional scale follows almost exactly that of the 334 mosquitoes, showing a deep split into sub-Sahara and North African fauna, followed by a further 335 split of sub-Saharan Africa into the West-Central Africa and the East-Southern African fauna 336 (Fig. 6b, top) . The MBP composition of West and Central Africa are most similar. The country-337 based dendrogram based on MBP composition reveals more pervasive cross-regional and 338 cross sub-divisions clusters. For example, North African countries are clustered together, but 339 Egypt is clustered with Tanzania (Fig. 6b) . Nonetheless, most countries are grouped by their 340 region or sub-division, i.e., West and Central African countries as well as East and Southern 341 African countries (Fig. 6b) . Departures from regional clustering often follows ecological similarity 342 between countries in the equatorial forests, (e.g., Cameroon and Ivory Coast). Assemblages of 343 MBPs defined by their significant co-occurrence in particular areas, independently from the 344 regions defined above are illustrated in Fig. S1b (Supp. Results and Discussion). 345 better knowledge of the African mosquito borne diseasosome, as a biological system, is 357 essential to improve local and global health and food security. To our knowledge, this study 358 provides the first holistic description of the biodiversity of mosquitoes and MBPs in any 359 continent. Despite scarce/incomplete information and historical unbalanced sampling efforts of 360 these taxa across Africa and the globe (below), the data recovered herein summarizes more 361 than a century of bio-surveillance efforts and is worthy of compilation and exploration to guide 362 future surveillance efforts by recognizing key knowledge gaps. Our results identify regions 363 expected to contain more sylvatic vectors of known and yet-to-be discovered MBPs and 364 advance understanding of the factors that have shaped the diversity of the African MBDs. Here, 365 we examine the process of range expansion of these diseases, as a key element of disease 366 emergence and interpret our results by addressing the following key questions: (i) Does 367 exceptional biodiversity of mosquitoes and MBPs in Africa account for its disproportionally larger 368 share as the origin of global MBDs and how likely is this trend to continue? (ii) What is the 369 geographical organization of mosquitoes and MBPs in Africa and has the former structured the 370 latter? and, (iii) What are the roles of domestication, dispersal, and adaptation to new vectors 371 and hosts as drivers of MBD range expansion? 372 A caveat of our analysis is the low resolution of the country-based distributional data. As cosmopolitan genera, such as Aedes, Culex, and Anopheles (Fig. 1a) , indicating no markedly 387 distinct fauna based on genera composition; yet, it has a distinct assemblage of subgenera ( Fig. 388 1b). Unlike mosquito diversity, the biodiversity of African arboviruses and (mammalian) 389 plasmodia-the largest taxonomic groups of MBPs (Fig. 1c) -are considerably greater than 390 expected by land mass at 30% and 40%, respectively (P<0.0001). These data support a 391 disproportionally higher diversity of MBPs in Africa than in any other continent. Avian plasmodia 392 could not be evaluated as explained above. The higher diversity of African MBPs (but not of 393 African mosquitoes) may account for the higher share of global MBDs originating in Africa and 394 in part for its disproportionally heavy burden of MBDs. While, we cannot rule out the possible 395 effect of greater sampling effort of MBPs in Africa compared with other continents. Yet, a recent 396 study reveals that sampling effort of emergent vector borne diseases has been lower in Africa 397 compared with other continents (Swei et al., 2020) . If the excess diversity of MBPs reported 398 here is correct, new global MBPs will continue to emerge from Africa at a higher rate than from 399 other continents, making Africa a prime target for future disease surveillance and control. 400 Unlike the mosquito fauna, which is mostly well described, the African MBPs remain poorly 401 known, given that 47% of the MBPs have been found in humans and domestic animals 402 whereas, at least 92% are maintained in wild species reservoirs (Fig. 1c) MBPs defined by their significant co-occurrence in the same countries ( With a quarter of the species occupying a single country, ~50% in 1-3 countries, and only 5% or 425 less present in >25 countries (Fig. 2) , most mosquitoes and MBPs occupy relatively small 426 ranges. Endemicity in African mosquitoes is lower than that reported globally (50%) (Foley et 427 al., 2007) , probably because African islands were excluded from our analysis. Based on the 428 median total area occupied by a mosquito and a species of MBP (see Results), their typical 429 ranges cover 10% and 7% of continental Africa, respectively. These range sizes can be 430 approximated by squares with sides of 1,760 km and 1,500 km, respectively. The distributions 431 of range size in African mosquitoes and MBPs are strikingly similar, although the mosquito 432 median is larger than that of the MBPs (see Results), suggesting that most African MBPs are 433 transmitted by one or just a few narrow-range mosquitoes in sylvatic cycles among their wild 434 host species. MBPs with one or few mosquito vectors are probably specialized to these vector 435 species and vertebrate hosts, whose ranges ultimately limit pathogen spread. Therefore, 436 adapting to multiple vector species is likely a prerequisite for initiating range expansion in MBPs 437 (see more below) and given the small number of domesticated mosquitoes (Fig. 2a) . Considering that the majority of the MBPs circulate in wild vertebrates (Fig. 1c) in a relatively 439 small area, this state might have represented the original phase of today's most widespread 440 MBPs (Fig. 2b) , which have since undergone range expansion. This may also apply to MBPs 441 that will emerge in the future (below (Fig. 2a) . These species feed preferentially on people 448 and/or domestic animals and are well adapted to the domestic environment. Notably, at least six 449 of these thirteen species were intercepted at high altitudes (40-290 m above ground) in the Similarly, the exceptionally widespread MBPs whose range exceed 20 countries include only 458 nine species (Fig. 2) These results assume that the distributions of the mosquitoes and (the known) MBPs is sound. 485 More comprehensive surveillance is expected to add distribution records and shift some of our 486 species to the right side of the L-shaped distributions (Fig. 2) . The fraction of country endemics 487 will probably decrease, but the L-shaped distribution may remain, because many newly 488 described MBPs of wild vertebrates with modest ranges will be added. Considering that only 489 part of a country is actually included in most species' ranges, accurate location data may 490 identify these parts, thus the net change in the typical range may be modest. species richness are similarly concentrated along the equatorial forest peaking in Central Africa. A secondary high "ridge" of high diversity stretches along the eastern coast from Kenya to South 497 Africa, whereas the lowest diversities are found across North Africa (Fig. 3) . Mosquito and MBP 498 exhibit corridors of moderate species-richness along the Sahel (Mauritania to Chad), and 499 between Central Africa and both East and Southern Africa (Fig. 3) . These corridors' continuity 500 and association to areas of seasonal aridity -inhospitable to mosquitoes, attest that they 501 represent natural features (below). Unlike species richness, mosquito endemicity reveals two or 502 three hotspots, whereas surrounding countries possessed few or no endemic species (Fig. 4) . 503 Endemic mosquito species are concentrated in the Cameroon and South Africa, followed by 504 Uganda, Kenya, Tanzania, Angola and the DRC. The African equatorial forest, which is known 505 for its high biodiversity combines stable conditions with diverse habitats, large area, and 506 mountains (>1,000 m above sea level) that promote speciation and accumulation of species 507 adapted to cooler habitats that found refuge in higher elevation (Lomolino 2020). Thus, higher 508 rates of speciation, lower rates of extinction, and high ecosystem diversity can explain the high 509 richness and endemicity of mosquitoes, MBPs (Figs. 3 and 4) , and vertebrate species (Burgess 510 et al. 2004 ). Somewhat different constellations of these factors extend the East and Southern 511 Africa around the Rift System, which can also explain its high biodiversity (Burgess et al. 2004 ). 512 Unlike the higher richness and higher endemicity region of Central Africa, the markedly low ratio 513 of endemicity to richness across Sahelian countries (Figs. 3 and 4) for long range migration. 523 The landscape of endemicity of MBPs shows a focal hotspot in Central African Republic, 524 towering over all countries (Fig. 4) . This exceptional endemicity is difficult to reconcile solely by 525 the effect of species richness and country's area (a determinant of the latter, Fig. 4) around these centers, leading to differences in virus diversity among countries. Regional 533 differences in diversity cannot be reconciled with these centers because the centers were 534 distributed across all regions. Between-region variation in surveillance effort is much smaller 535 than that between countries, therefore, regional analysis is used to test the main country-based 536 results. For example, the higher fraction of region vs. country endemicity (40% vs. 25%) of the 537 mosquito and MBP species, finding 60% of the mosquitoes and MBPs in one or two regions, 538 and only 3% (mosquitoes) and 11% (MBPs) across the continent (Fig. 5) are consistent with 539 country-based results. Additionally, despite sharing ecozones and biomes across our regions 540 (Burgess et al., 2004 ), the regional analysis revealed compositional heterogeneity in mosquitoes 541 and MBPs across the continent (Figs. 5, 6) . The country dendrograms based on composition of 542 mosquitoes and MBPs generally clustered together countries of the same subdivisions (Fig. 6) . 543 Remarkably, the clustering of regions into subdivisions based on the composition of the 544 mosquito and MBP faunas were nearly identical (Fig. 6 ). Similar to plant and vertebrate 545 biogeographical results (Burgess et al., 2004) our sub-Saharan Africa and North Africa divisions 546 (Fig. 6 ) match the Palearctic and the Afrotropical faunal realms and highlight the Sahara as a 547 geographic barrier. Clustering West and Central Africa regions together, separately from the 548 cluster of East and Southern Africa (Fig. 6) fits also with the vertebrate biogeographical 549 landscapes including those of mammals and birds (Burgess et al., 2004) . Our West and Central 550 regions share the Sudanian, Sahelian and Equatorial (Guinean-Congolian) zoogeographical 551 zones whereas our East and Southern Africa regions overlap with the Zambezian and South 552 African zoogeographical zones (Linder et al., 2012) . The high mountains along the Rift System 553 probably contribute to the separation between the East and Central regions. The clustering of 554 countries based on mosquito composition indicated a subdivision of our West and Central 555 African regions into Sudano-Sahelian and Equatorial subregion as indicated by grouping of 556 Chad with Niger and Ivory Coast with Central African Republic (Fig. 6) showing correspondence 557 between our results and the zoogeographical zones identified by Linder et al. (2012) . Altogether 558 these corresponding patterns add support for a strong bio-geographical signal in our results. 559 As for the distribution of range area (above), the regional composition of the MBPs was nearly 560 identical to that of the mosquitoes, raising the question "Has MBPs geographical organization richness and endemicity using the same unit area, which is beyond our analysis and data. 572 The high similarity in geographic organization of African MBPs and mosquitoes (Figs. 2-6 and 574 S1a), and the facts that most MBPs circulate in wild vertebrate hosts (Fig. 1d) within a narrow 575 distributional range -remarkably similar to that of mosquitoes (Fig. 2) Once the MBP attains transmissibility into and from human or domestic animals by at least one 602 of the domesticated vectors, the transition into the last phase is complete and a rapid final range 603 expansion is expected worldwide. Accordingly, a larger than typical geographical range is a marker of a MBP in the intermediate 606 phase (above), in which the MBP has expanded its vector and/or vertebrate range. Except for 607 small coastal ecozones, the African biogeographical units are typically wider across their east-608 west axis than across their north-south axis (Burgess 2004) , suggesting that the longer the 609 north-south dimension of a MBP's range, the more likely it is to be transmitted by multiple vector 610 species across multiple host species. Hence, we propose that MBP total range size, estimated 611 as the sum of the area (of the countries) in their range and maximal north-south length of their 612 range be used to gauge its range expansion phase. Whereas these range size measures are 613 expected to be largest in MBPs circulating among humans and domestic animals and smallest 614 for those circulating in wild mammals, it is less clear if MBPs circulating in wild birds are larger 615 than those of wild mammals. Both measures were larger for MBPs circulating in humans and 616 domestic animals for the median and the 75 th quantile (area: P<0.0001, t>8 df=116, north-south: 617 P<0.0001, t>5 df=116, Figs. 7a, 7b), but no significant differences were found between MBPs 618 circulating in mammals and birds even using one side test (area: P>0.31, t<0.11 df=116, north-619 south: P>0.11, t<1.2 df=116, Figs. 7a, 7b). Contrary to our expectation, the north-south distance 620 seems to "saturate" faster than the total area (Fig. 7) , indicating that it may be more sensitive to 621 early range expansion than to later stages of MBD range expansion. The total area of most 622 MBPs transmitted among humans or domestic animals (undergone range expansion, N=15) 623 cover area 10-20 x10 6 km 2 and their north-south distance spans 40-60°, whereas the majority 624 of MBPs (>90) cover <4 x10 6 km 2 and north-south distance >15° (Fig. 7c) . Except eight MBPs 625 transmitted among wild birds that have a long north-south distance, 30 MBPs occupy 626 intermediate ranges covering area 4-10 x10 6 km 2 and north-south distance of 20-50° (Fig. 7c) . (SPOV), and ONNV, which are elevated for both measures (Fig. 7c) . This approach putatively 631 identifies expanding pathogens during the intermediate phase of range expansion even before 632 they infect humans or domestic animals. Monitoring changes in geographical range as well as 633 the MBP host range and vector range would be key to evaluating these aspects of disease 634 emergence. Validating this biogeographical ranking with independent risk predictions will 635 increase confidence in the subset of MBPs of elevated risk. For example, the number of vectors 636 and hosts in which a pathogen is found in and the numbers it can be transmitted from may be 637 used as independent markers of the MBP's prospects to undergo further range expansion. 638 Experimental evidence about the pathogen compatibility and capacity for transmission e.g., 639 (Haddow et al., 2016) with the most widespread vectors and domestic hosts (Fig. 2) , will further 640 augment the risk assessment. Development and testing of such models will advance 641 understanding and predictive capacity of range expansion as a component of disease 642 emergence. Evaluation of the pathogenicity and impact that a MBP would have on human and 643 domestic animals are beyond the scope of this analysis, but the possibility of increased 644 virulence linked to transmissibility in these new hosts by domesticated vectors, e.g., ZIKV -645 should not be ignored. 646 Figure 7 . Ranking of African mosquito-borne pathogens by their range area and maximum north-south distance to 647 estimate their phase of range expansion. a) Variation between host groups in north-south distance (latitude degrees) 648 and b) Variation between host groups total range area (10 6 km 2 ). c) relationship between MBP's total area (10 6 km 2 ; 649 X-axis) and the maximum north-south distance (degrees latitude; Y-axis) using local regression (loess and 95% CLM) 650 on all MBDs (N= 150). Box plots along axes display distributions of corresponding variables. Acronym of MBPs are 651 given for those with total area larger than 2.5 or north-south longer than 5° and colors denote host group (birds were 652 used if birds and mammals are thought to act as natural hosts). Box draws attention to putative MBPs at intermediate 653 phase of range expansion (excluding MBPs of birds and domestic animals, see text). The database and our analysis refer to continental Africa (surrounded by the Mediterranean Sea 657 to the north, the Indian Ocean to the east and the Atlantic Ocean to the west), excluding all 658 islands (e.g., Cape Verde, Comoros, Madagascar, Mauritius, Seychelles, São Tomé and 659 Príncipe) because island biogeography requires consideration of multiple factors, such as 660 distances to the nearest mainland and to other islands, historical formation of the island, 661 existence of past terrestrial bridges, etc., which deserve a separate treatment. Very few records 662 of mosquitoes and MBPs can be found for Eswatini, Lesotho, South Sudan and Western 663 Sahara. Moreover, parts of their records are included in their previous political affiliations, e.g., 664 South Sudan in Sudan. Therefore, these countries are not listed in our analysis; instead, our 665 analysis, pertains to 45 countries, with few countries that subsumed those in the past and still 666 "contain" their records, e.g., "Sudan and South Sudan" being used (Table S1 ). Because 667 countries differ in surveillance effort, grouping neighboring countries into regions minimizes 668 variation in surveillance effort variability and was used to test country-based patterns. Unlike the 669 geopolitical regions with the same names, our five regions were defined to maximize distances 670 among regions, accommodate latitudinal variation, and minimize inter-region enclaves (Fig. 5) . (Jupp, 1996) . 676 Information on global diversity of mosquitoes was recently updated (Wilkerson et al., 2021) and 677 allowing reconciliation of species identifications that were later revised, e.g., Culex tigripes and 678 Lutzia tigripes or An. arabiensis and An. gambiae. Subspecies were not included in our data. 679 The mosquito-borne pathogen (MBP) distribution data was generated based on hundreds of 680 references listed in Supp File 2, providing they met the three criteria as follows: A peer-reviewed 681 scientific source (or a source, e.g., the CDC arbovirus catalogue, listed in peer-reviewed 682 sources) reported that the MBP has been i) naturally transmitted in continental Africa, ii) to a 683 terrestrial vertebrate host, iii) by mosquito vector, to the extent that this mode of transmission is 684 recognized to have an epidemiological role, even if other mode(s) of transmission play a greater 685 role. Our database includes information whether mosquito role in the MBP transmission is 686 secondary or primary and whether it is biological or mechanical. Strains or any sub-species 687 definitions were not included in our analysis. among other sources. Only records that met our above criteria were included in our database. 692 By confining our records to continental Africa, the term endemic refers to a species found in one 693 African country (or region, when specified), however, although uncommon, the species may be 694 also found outside continental Africa. Supplemental Results and Discussion 747 The similarity in species richness of MBPs and mosquitoes (Fig. 3) is also expressed by the 748 high positive correlation coefficient between these indices (r= 0.76, N= 45, P< 0.001 Fig. S1a) , 749 although the correlation in species endemicity was far lower (r= 0.26, N= 45, P= 0.09, Fig. S1b ). Because conventional pathogen detection requires species-specific diagnostic test that have 751 been developed for common and widespread pathogens, endemic pathogens are expected to 752 be under-detected. Furthermore, this weak correlation may also reflect sampling effort inequality 753 of uncommon MBPs among countries (see Main text). 754 Although the overall regional distributions of mosquitoes and MBPs are very similar (Fig. 5) , the 755 differences (Fig. S1c ) reveal a higher fraction of cross-Sahara MBPs (found in all five regions), 756 whereas a higher fraction of mosquitoes if found across sub-Saharan Africa (P< 0.01, Fig. S1c ). This pattern suggests that relatively few MBPs, albeit more than mosquitoes, are transported by 758 their vertebrate host(s) across the Sahara. Additionally, MBPs that have been recently 759 introduced into Africa, eg., DENV, may have been arrived into multiple parts of the continent, 760 and being already adapted to the domestic environment, may have spread rapidly. Unlike 761 pathogens that are easily transported by human and domestic animals, fewer mosquitoes 762 represent this subgroup, e.g., Ae. albopictus and An. stephensi. 763 because it is not the primary mode of pathogen transmission (Fig. 1c) , which perpetuates this 774 attitude despite limited information about it. In Africa, only pox viruses and bacteria are reported 775 to be transmitted mechanically by mosquitoes (Fig. 1c) . The epidemiological contribution of 776 mosquito transmission of these MBPs in short-and long-range spread of the pathogens is 777 poorly known (but see main text), as well the extent of the vector range used by these 778 pathogens. Further study and surveillance of pathogens transmitted mechanically by 779 mosquitoes (especially bacteria) would reveal new grounds. 780 Species that co-occur more than expected by chance define regional assemblages that can 782 underlie similar ecological preferences or co-dependence. We used Veech co-occurrence index 783 (Veech, 2013) to evaluate which pairs of species co-occur positively across countries (joint 784 country occurrence is higher than expected by chance), negatively (joint country occurrence is 785 lower than expected by chance), or randomly (joint country occurrence is not different than 786 expected by chance across 40 countries. Negative co-occurrence in mosquitoes were especially common in 793 Anopheles (78%) and Culiseta (6%), both within and across genera, whereas positive co-794 occurrences between species pairs were distributed across all genera (not shown). Such 795 negative association suggests adaptive speciation in distinct environments, where assemblages 796 are unique, and therefore not overlapping in species composition. Anopheles and Culiseta have 797 the highest fraction of African species among the genera (except Eretmapodites, which is 798 mostly equatorial; see Results), suggesting extensive speciation in Africa and distinct 799 environment that supports this explanation. 800 Considering MBPs in the whole continent, 17.4% (315) of the pairs were positive and 0.2% (4) 801 were negative out of a total of 1,807 testable pairs (Fig. S2b: inset) . Because 17% of species 802 are found across the Sahara, rather than the corresponding 5% of the mosquitoes (above), 803 North African countries were included in subsequent analyses. Unlike the negative co-occurring 804 MBP pairs, the number of positive co-occurring MBP pairs is far higher than that expected by 805 chance (2.5%). 806 To visualize the organization of mosquito assemblages, defined by the co-occurrence analysis, 807 positively co-occurring pairs of narrow-range species (5-10 countries) were included in a 808 network consisting 119 pairs (Fig. S2a) . The mosquito network exhibited four disjointed 809 components, reflecting distinct assemblages: (i) Western-Central Africa cluster represented by 810 Cx. subrima (main) with an equatorial cluster represented by Ae. abnormalis, (ii) Southern-East 811 Africa represented by An. confusus, (iii) Southern-Central Africa, represented by An. walravensi, 812 and (iv) a small widespread assemblage, represented by Ae. capensis (Fig. S2a) . 813 The network of 53 MBPs pairs consisting of 25 species, (5-10 countries) presented a single 814 component (Fig. S1b) . While more densely connected than the mosquito network (density: 815 0.177 vs. 0.059), distinct yet partly-overlapping assemblages are found in Southern-East and 816 Central Africa represented by Bwamaba/Ndumu viruses (Fig. S2b, Because mosquito transmission is the primary route of vertebrate infection in >90% of MBPs 833 (Fig. 1c) , high vector-specificity is expected for sylvatic vectors, except for the poxviruses and 834 the three bacteria that rely on mechanical transmission. A bipartite network of mosquitoes and 835 MBPs based on the Veech index can reveal assemblages of mosquitoes and pathogens, which 836 might be different than their within-group assemblages. Albeit based on geography alone, 837 linking mosquitoes and MBPs may also help identify subset of putative sylvatic mosquito 838 vectors, which can be further refined applying other selective criteria. Veech co-occurrence 839 analysis (over the whole continent) revealed that 83% of the testable pairs were random, 16% 840 were positive and 1% were negative at P<0.05 (N= 21,342 testable mosquito-MBP pairs). 841 Considering only highly positively co-occurring pairs (P<0.01; note: 2.5% of the total tests at 842 each side are expected by chance), a bipartite network comprising of 30 MBPs and 80 843 mosquitoes with 194 links was plotted (Fig. S3) . To simplify interpretation, mechanically-844 transmitted MBPs and non-blood-feeding mosquitoes were excluded and only pairs in which the 845 pathogen joint co-occurrence was fully subsumed in that of the mosquito were retained. The 846 largest MBP-mosquito assemblages were from Central Africa: Plasmodium gonderi (PLGO with 847 19 mosquitoes), Pl. reichenowi (PLRE), followed by that in Southern-East and Central Africa 848 Bwamaba virus (BWAV, Figs. S2, S3). 849 This network includes broad-ranging MBPs, e.g., Pl. malariae, whose range is subsumed only in 854 that of An. funestus (Fig. S3) . On average each MBP is linked to 6.5 mosquitoes (median= 6). 855 Because geographical overlap in MBP and mosquito distribution is the only basis for linking 856 them, the matrix included 5 non-bloodfeeding mosquitoes (Ml. fraseri, Ml. moucheti, Tr. aeneus, 857 Tr. viridibasis, and Tr. wolfsi, not shown). Likewise, the links between Pl. reichenowi, which is 858 thought to be transmitted exclusively by Anopheles mosquitoes also include 15 culicines. 859 Therefore, incorporating additional criteria such as Anopheles to filter among putative vectors of 860 a mammalian Plasmodium species, incorporating information on bloodmeal host range, and 861 permitting partial range overlap can produce a more accurate list of putative mosquito vector 862 species for surveillance and vectorial competence experiments. This approach can help 863 identifying the sylvatic vectors of many pathogens. 864 865 The probabilistic model of species co-occurrence (Veech, 2013 ) was used to classify pairs of 867 species co-occurrence as negative, positive or random based on the probabilities that two 868 species would co-occur at a frequency less than or greater than the observed frequency if the 869 two species were distributed independently of one another among sites. Veech index is based 870 on an analytic probabilistic model using combinatorics to obtain the probability that two selected 871 species co-occur at any given number of sites among those sampled. Progress in understanding the 885 phylogeny of the Plasmodium vivax lineage MalAvi: a public database of malaria parasites 887 and related haemosporidians in avian hosts based on mitochondrial cytochrome b lineages Emerging infectious diseases: Public 890 health issues for the 21st century Mosquito-borne arboviruses of African origin: Review of key viruses and vectors. Parasites and 893 Vectors Terrestrial eco-regions of Africa and Madagascar: A conservation assessment How many species of mammals 898 are there The evolvability of emerging viruses Arbovirus Catalog [WWW Document Field Guide to the Frogs & Other Amphibians of Africa Penguin Random House South Africa Seasonal migration to high latitudes results in major reproductive benefits in an insect Plasmodium ovale: Parasite and disease The igraph software package for complex network research The role of Culex tarsalis in the transmission of fowl pox virus 916 (2021) Population genomic evidence of Plasmodium vivax Southeast Asian origin Landscape 921 ecology of sylvatic chikungunya virus and mosquito vectors in southeastern senegal Zika virus 924 emergence in mosquitoes in Southeastern Senegal Mosquito vectors of the 926 1998-1999 outbreak of Rift Valley Fever and other arboviruses (Bagaza, Sanar, Wesselsbron 927 and West Nile) in Mauritania and Senegal Introducing the bipartite 929 package: analysing ecological networks Insect migration: tracking resources through space and 931 time Radar entomology : observing insect flight and migration. 933 CAB International Zika virus: An updated review of 935 competent or naturally infected mosquitoes Sentinel site-enhanced near-real time 937 surveillance documenting West Nile virus circulation in two Culex mosquito species indicating 938 different transmission characteristics Number 3-March 2014 -942 Emerging Infectious Diseases journal -CDC. Emerging Infectious Diseases Emerging infectious diseases in Africa in the 21st 944 century Diversity, 946 dynamics, direction, and magnitude of high-altitude migrating insects in the Sahel Insight into Global Mosquito Biogeography 949 from Country Species Records New vectors of Rift Valley fever in West Africa A dispersion of mosquitoes by wind The possibility of active long-distance migrations by Anopheles 954 pharoensis Theobald Countries: Public data [WWW Document Ecology drives the worldwide distribution of 958 human diseases Genetic Characterization of Spondweni and Zika Viruses and Susceptibility of Geographically 961 Distinct Strains of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus (Diptera: 962 Culicidae) to Spondweni Virus Valley Fever Virus Epidemic in Kenya Detecting shifts of transmission areas in avian blood parasites -a phylogenetic 968 approach Windborne 970 long-distance migration of malaria mosquitoes in the Sahel Updated list of Anopheles species 972 (Diptera: Culicidae) by country in the Afrotropical Region and associated islands 975 Global trends in emerging infectious diseases Local adaptation and vector-mediated population structure in Plasmodium vivax malaria Aedes furcifer and other mosquitoes as vectors of chikungunya 980 virus at Mica, northeastern Transvaal, South Africa Mosquitoes of Southern Africa: Culicinae and Toxorhynchitinae Am Soc Trop Med Hygi for the Subcommittee on Information Exchange of 985 the Am Comm on Arthro born viruses Mosquito (Diptera: Culicidae) Dispersal: Implications for the 987 Epidemiology of Japanese and Murray Valley Encephalitis Viruses in Australia Transmission of fowl-pox by mosquitoes A geo-992 coded inventory of anophelines in the Afrotropical Region south of the Sahara The global dispersal of bancroftian filariasis Mosquitoes (Diptera: Culicidae) in Mauritania: A review of their biodiversity, distribution and 998 medical importance. Parasites and Vectors Avibase -The World Bird Database [WWW Document The 1002 partitioning of Africa: statistically defined biogeographical regions in sub-Saharan Africa Climate and satellite indicators to forecast Rift Valley fever epidemics in Kenya Rift Valley fever virus Isolations from Diptera collected during an inter-epizootic 1009 period in Kenya Origin 1011 of the human malaria parasite Plasmodium falciparum in gorillas Biogeography A Very Short Introduction. First Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key 1016 theory Plasmodium falciparum evades immunity of anopheline mosquitoes by interacting 1019 with a Pfs47 midgut receptor The human malaria parasite Pfs47 gene mediates evasion of the mosquito immune system Could culicine mosquitoes transmit human 1025 malaria? Prediction and prevention of the next pandemic zoonosis A Systematic Review of the Natural Virome of 1029 Anopheles Mosquitoes Arboviruses isolated from 1031 the Barkedji mosquito-based surveillance system 1034 (2009) Coquillettidia (Culicidae, Diptera) mosquitoes are natural vectors of avian malaria in 1035 Long-range insect migration in relation to 1037 climate and weather: Africa and Europe Malaria's Many Mates: Past, Present, and Future of the Systematics of the 1041 Order Haemosporida Malaria in Farmed Ungulates: an Exciting New System for Comparative 1043 Parasitology. mSphere 1045 (2019) Spatial and Temporal Variability in Migration of a Soaring Raptor Across Three 1046 Continents Partial migration in savanna 1048 elephant populations distributed across southern R: A Language and Environment for Statistical Computing The migration of insect vectors of plant 1051 and animal viruses A migration of grasshoppers 1056 (2017) Avian migration and the distribution of malaria parasites in New World passerine birds Detecting the emergence of novel, zoonotic viruses pathogenic to 1059 humans Search strategy has 1061 influenced the discovery rate of human viruses 1064 (2017) Plasmodium malariae and P. ovale genomes provide insights into malaria parasite 1065 evolution The effects of 1067 high-altitude windborne migration on survival, oviposition, and blood-feeding of the African 1068 malaria mosquito, Anopheles gambiae s.l. (Diptera: Culicidae) SAS software for Windows Version 9 Weather, host and vector--their interplay in the spread of insect-borne 1072 animal virus diseases Encyclopedia of Arthropod-transmitted Infections Role of Culex and Anopheles mosquito species as potential 1076 vectors of rift valley fever virus in Sudan outbreak Human Migration and the Spread of the Nematode Parasite Wuchereria bancrofti Migration of terrestrial arthropods in relation to habitat 2020) Patterns, Drivers, and 1083 Challenges of Vector-Borne Disease Emergence. Vector-Borne and Zoonotic Diseases Mosquitoes 1086 (Diptera: Culicidae) and mosquito-borne diseases in Mali A Review of Mosquitoes Associated with Rift 1089 Valley Fever Virus in Madagascar Risk factors for human disease 1092 emergence Data: Land Area [WWW Document Conservation status 1097 and threats for African reptiles An updated checklist of the Culicidae (Diptera) of with notes on species of historical and current medical importance Mechanical transmission of Bacillus anthracis by stable 1102 flies (Stomoxys calcitrans) and mosquitoes (Aedes aegypti and Aedes taeniorhynchus) Growing evidence of Plasmodium vivax across malaria-endemic Africa. PLOS Neglected 1106 Tropical Diseases Mosquitoes put the brake on arbovirus evolution: Experimental evolution reveals slower 1109 mutation accumulation in mosquito than vertebrate cells Exploiting the Legacy of the Arbovirus Hunters A probabilistic model for analysing species co-occurrence Arbovirus and insect-specific virus discovery in Kenya by novel six genera multiplex high-1116 resolution melting analysis Database of host-1118 pathogen and related species interactions, and their global distribution Chikungunya virus: Role of vectors in emergence 1121 from enzootic cycles Alphaviruses: Population 1123 genetics and determinants of emergence Vector-borne diseases [WWW Document Origins of major human infectious 1129 diseases Host range and emerging and reemerging 1131 pathogens