Secondary amplification in domestic animals

Some arboviruses can achieve higher levels of circulation and infect more humans via secondary amplification in domestic animals. The phlebovirus (Bunyaviridae) Rift Valley fever virus is a good example; this virus is maintained primarily in sub-Saharan Africa by horizontal and transovarial transmission in mosquitoes, including Aedes and Culex spp. [2, 15]. Epizootics usually follow unusually heavy rainfall and involve infection of domestic ruminants including cattle, goats and sheep, resulting in high levels of horizontal transmission by mosquitoes to both domestic animals and humans, as well as direct human infections from the slaughter and handling of infected animals. This secondary amplification and transmission can result in epidemics in very arid locations not normally subject to arboviral outbreaks, such as Saudia Arabia [14].

Another example of secondary amplification resulting in human arboviral disease is Japanese encephalitis virus, a flavivirus that occurs in Asia and Oceania. Aquatic birds are the normal reservoir hosts and culicine mosquitoes that bite a viremic bird can infect humans, sometimes resulting in severe neurological disease, primarily in children [1, 5]. In many endemic locations, pigs are raised for food in close proximity to human habitations. When infected by a mosquito bite, pigs do not develop apparent disease but do become viremic, resulting in peridomestic amplification and increased risk for human infections (Fig. 1).

The above examples involve amplification of arbovirus transmission via domestic animals that are susceptible to most or all strains circulating. A more complex example is VEEV, a species including many serotypes that circulate

Spiny rats, cotton rats, etc.

Spiny rats, cotton rats, etc.

Epizootic Versus Enzootic

Fig. 3. Cartoon depicting transmission of Venezuelan equine encephalitis virus. The enzootic cycle at the left generally occurs in lowland tropical forest or swamp habitats where various members of the Spissipes section of the Culex (Melanoconion) subgenus transmit virus among rodent reservoir hosts. Human infection can occur via direct spillover when people enter enzootic foci and are bitten by enzootic vectors, which tend to have broad host ranges. Equine epizootics and epidemics involving up to hundreds-of-thousands of cases occur when enzootic ID strains mutate to generate the IAB or IC epizootic serotype and enhance their ability to produce equine viremia. This leads to intense transmission in agricultural settings, resulting in spillover to humans. Humans also develop high titered viremia and are therefore potentially capable of amplification, but epidemiological studies indicate no evidence of transmission in the absence of equines; this suggests that humans play a minor role as amplifiers

Fig. 3. Cartoon depicting transmission of Venezuelan equine encephalitis virus. The enzootic cycle at the left generally occurs in lowland tropical forest or swamp habitats where various members of the Spissipes section of the Culex (Melanoconion) subgenus transmit virus among rodent reservoir hosts. Human infection can occur via direct spillover when people enter enzootic foci and are bitten by enzootic vectors, which tend to have broad host ranges. Equine epizootics and epidemics involving up to hundreds-of-thousands of cases occur when enzootic ID strains mutate to generate the IAB or IC epizootic serotype and enhance their ability to produce equine viremia. This leads to intense transmission in agricultural settings, resulting in spillover to humans. Humans also develop high titered viremia and are therefore potentially capable of amplification, but epidemiological studies indicate no evidence of transmission in the absence of equines; this suggests that humans play a minor role as amplifiers enzootically in much of Latin America, where they infect rodent reservoir hosts in stable forest or swamp transmission foci (Fig. 3) [34]. The mosquito vectors of these enzootic strains generally remain in the forest or swamp habitats. Therefore, human infection via direct spillover is usually limited to enzootic habitats, and large epidemics involving direct spillover have not been reported. However, certain epizootic strains of VEEV, comprising serotypes IAB and IC, produce massive epidemics and equine epizootics involving up to hundreds-of-thousands cases over a period of a few months to a few years. These strains achieve widespread and intense circulation by infecting equines and producing high titer viremia.

When large salt marsh or floodwater mosquito populations are present during rainy seasons, equines are extremely attractive hosts and an infected animal can generate hundreds of infectious mosquito vectors following blood feeding and extrinsic incubation, resulting in infection of additional equines as well as humans who live in agricultural settings (Fig. 3). However, epizootic transmission is unstable and is usually interrupted when most or all equines become infected and die or survive with immunity, and/or when mosquito populations decline following the onset of a dry season. Intervals of up to 19 years between outbreaks without evidence of serotype IAB or IC VEEV circulation in nature, led to investigations of the relationships between enzootic and epizootic strains. Evidence has accumulated supporting the hypothesis that one of many enzootic subtype ID lineages periodically mutates to produce the epizootic strains that initiate outbreaks [11, 20, 22, 23]. None of the enzootic variants is capable of amplifying in equines in their normal state [26, 32], so the generation of epizootics relies on small numbers of critical mutations in the E2 envelope glycoprotein of the enzootic progenitors that augment the ability of VEEV to produce equine viremia [6a]. Other evidence indicates that, in some cases, VEEV adapts to infect more efficiently the epizootic mosquito vectors that transmit during outbreaks. This adaptation is also mediated by mutations in the E2 glycoprotein that forms the spikes on the virion surface and probably interacts with specific cellular receptors of equines and mosquitoes [3, 4, 6a].

As mentioned above, it is unknown whether other arboviruses, such as EEEV, have the potential to adapt for amplification in domestic animals such as RVFV, JEV and VEEV. Understanding the genetic basis of arboviral host range and viremia phenotypes is critical to assessing the potential for future epidemics via secondary amplification in domestic animals.

Was this article helpful?

0 0

Post a comment