Braack et al. Parasites & Vectors (2018) 11:29 DOI 10.1186/s13071-017-2559-9 REVIEW Open Access Mosquito-borne arboviruses of African origin: review of key viruses and vectors Leo Braack1* , A. Paulo Gouveia de Almeida2,3, Anthony J. Cornel1,4, Robert Swanepoel5 and Christiaan de Jager6 Abstract Key aspects of 36 mosquito-borne arboviruses indigenous to Africa are summarized, including lesser or poorly-known viruses which, like Zika, may have the potential to escape current sylvatic cycling to achieve greater geographical distribution and medical importance. Major vectors are indicated as well as reservoir hosts, where known. A series of current and future risk factors is addressed. It is apparent that Africa has been the source of most of the major mosquito-borne viruses of medical importance that currently constitute serious global public health threats, but that there are several other viruses with potential for international challenge. The conclusion reached is that increased human population growth in decades ahead coupled with increased international travel and trade is likely to sustain and increase the threat of further geographical spread of current and new arboviral disease. Keywords: Africa, Mosquito-borne arboviruses, Vector mosquitoes, Zoonoses, Global health threats Background United Nations projections indicate a likely increase in Epidemics in recent years of Zika virus (ZIKV) in South global human population from current > 7 billion people and Central America [1–3] and yellow fever virus (YFV) to a probable peak of around 9.6 billion in 2050 [24]. in Africa [4] and Brazil [5–7] serve as reminders of the The consequences of such population increase will likely dramatic manner in which apparently quiescent or stable favour the spread and impact of zoonoses. Large human zoonoses can flare up or spread with serious international population increases will be associated with increasing public health, social and economic consequences. These population density which facilitates transmission of virus events are steadily increasing in frequency, involving path- either directly or through vectors. There will also be ogens which establish foothold in new geographical terri- increased international movement of people by way of tories where they become endemic after initial rapid migration, tourism or business travel thereby increasing spread. Examples include yellow fever introduced to the the likelihood of more frequent dissemination of infect- New World from Africa in the early 1600s with subse- ive sources. Similarly, there will be increased global quent major impact [8–10], dengue virus which spread as movement of cargo and trade goods facilitating the different antigenic variants from its probable Asia-Pacific spread of vectors, increased land transformation and dis- origin to the Americas in the 1960s and Africa in the ruption of historical ecological processes which pro- 1980s [11–13], chikungunya which arose in Africa to simi- motes contact between humans and infected wildlife or larly invade extensive new areas in the mid-2000s [14–18], sylvatic vectors. Finally, increased human population will West Nile virus which caused a stir when first diagnosed also increase breeding site and habitat formation for in the USA in 1999 and soon spread to Canada and Cen- virus vectors such as Aedes aegypti and Aedes albopic- tral America [19, 20], and most recently Zika virus with tus, especially in expanding urban environments. A dis- an epidemic in Micronesia in 2007 [21], French Polynesia proportionately high percentage of the mosquito-borne in 2013 [22] and South America in 2015 [23]. arboviruses currently having serious public health impact at global scale is of African origin. In addition to this subset of arboviruses, there is substantial evidence by way of sero- prevalence studies of a wide range of other arboviral infec- * Correspondence: [email protected] 1School of Health Systems & Public Health, University of Pretoria, Pretoria, tions which - like Zika virus in Africa historically - are South Africa circulating within immunologically-adapted indigenous Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Braack et al. Parasites & Vectors (2018) 11:29 Page 2 of 26 African populations largely having little history of serious the mosquito-borne viruses. Ticks change hosts and symptoms. These include Banzi [25, 26], Bwamba [27–32], have blood-meals relatively infrequently whereas mos- Bunyamwera [29, 30, 33–35], Germiston [34, 36], Ilesha quitoes have multiple blood-feeds off more hosts in a [37], Lumbo [38], Middelburg [35], Ndumu [39, 40], Ngari much shorter time span with greater movement over a [41–43], Ntaya [44], O’nyong-yong [45], Pongola [29, 30, landscape given their ability to fly. Mosquito-borne 35], Rift Valley fever [46, 47], Semliki Forest [35], Shuni viruses thus have greater opportunity to mutate and [48], Simbu [35], Sindbis [35, 49], Spondweni [50, 51], spread across shorter generational spans within a greater Uganda S [52], Wesselsbron [29, 30, 34, 35] and number of hosts, thereby facilitating evolutionary diver- Witwatersrand viruses [53]. Given the preponderance of sification. Medically-important mosquito-borne flavi- zoonoses of African origin that have escaped previous viruses can be sub-clustered into two groups. One group endemic African settings to make geographical jumps to comprises viruses associated with Aedes mosquitoes other regions through anthropogenic processes that are several of which cause haemorrhagic disease in primates. likely to escalate, this paper focuses on the subset of The other group subdivided into predominantly Aedes- mosquito-borne arboviral zoonoses that are already known transmitted viruses often also causing haemorrhagic to exist in Africa, either with potential for continuing symptoms, and predominantly Culex-transmitted viruses expansion of range or of which very little is known except often associated with encephalitic disease [55]. Phylo- that they infect humans or have genetic affinities which genetic analyses suggest multiple introductions of arbo- suggest they may infect humans. When entering immuno- viruses from the Old World to the New World in recent logically naïve populations in new geographical settings the millennia and that the most parsimonious explanation public health consequences are difficult to predict. for current genetic distributions indicates an “Out-of-Af- Below we provide an outline of the relevant virus rica” ancestry; all of the Culex-associated flaviviruses groups and specific viruses that are known to have pub- currently circulating in Asia, Australia, Europe and the lic health risk or could have public health importance in America’s appear to have evolutionary roots in Africa future, including the mosquito species involved in trans- [56]. It has also been posited that, like yellow fever virus, mission or found infected with these viruses. dengue virus similarly had its origin in Africa and was frequently transported to the America’s during the slave Synoptic overview of the African mosquito-borne period [57, 59]. Other more deeply rooted ancestral lines arbovirues of medical importance of viruses dating back 2000 to 3000 years appear to Mosquito-borne viruses affecting humans are concen- have dispersed eastwards out of Africa and given rise trated in three families, the Flaviviridae (genus Flavivirus), to Japanese encephalitis virus, Murray Valley enceph- Togaviridae (genus Alphavirus), and the Bunyaviridae alitis virus and others [56]. (primarily genus Orthobunyavirus but with a few import- ant outliers such as the Phlebovirus Rift Valley Fever). For Banzi virus (BANV) the African region, the individual viruses and their Banzi virus was first isolated in 1956 from the blood categorization, together with key attributes, are summa- of a febrile child in South Africa [25] and subse- rized in Table 1. Below follows a summary overview of the quently confirmed from a febrile patient in Tanzania virus families and the known African mosquito-borne ar- [60]. Seroprevalance studies have shown BANV to be boviruses in those families; the arrangement is the same as widely distributed across southern Africa including in Table 1, i.e. alphabetically within family for ease of find- Angola, Botswana, Mozambique, Namibia and South ing and not clustered into serogroups. Africa [25, 34]. BANV has been repeatedly isolated from wild-caught Culex rubinotus [49, 61] which is Flaviviridae regarded as the primary vector of this virus [62]. Phylogenetic trees suggest that Africa was the ancestral Rodents are believed to be the natural host [63]. origin of all mosquito and tick-transmitted flaviviruses Culex rubinotus is widely distributed in Africa and [54–56], probably from what were initially non-vectored abundant in subtropical coastal marshlands [62]. This mammalian viruses [55]. Flavivirus members are readily mosquito appears to maintain