Heartland Virus Epidemiology, Vector Association, and Disease Potential

Abstract

First identified in two Missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne phlebovirus producing similar symptoms in China, Korea, and Japan. Field isolations of HRTV from several life stages of unfed, host-seeking Amblyomma americanum, the lone star tick, implicated it as a putative vector capable of transstadial transmission. Laboratory vector competence assessments confirmed transstadial transmission of HRTV, demonstrated vertical infection, and showed co-feeding infection between A. americanum. A vertical infection rate of 33% from adult females to larvae in the laboratory was observed, while only one of 386 pools of molted nymphs (1930) reared from co-feeding larvae was positive for HRTV (maximum-likelihood estimate of infection rate = 0.52/1000). Over 35 human HRTV cases, all within the distribution range of A. americanum, have been documented. Serological testing of wildlife in areas near the index human cases, as well as in widely separated regions of the eastern United States where A. americanum occur, indicated many potential hosts such as raccoons and white-tailed deer. Attempts, however, to experimentally infect mice, rabbits, hamsters, chickens, raccoons, goats, and deer failed to produce detectable viremia. Immune-compromised mice and hamsters are the only susceptible models. Vertical infection augmented by co-feeding transmission could play a role in maintaining the virus in nature. A more complete assessment of the natural transmission cycle of HRTV coupled with serosurveys and enhanced HRTV disease surveillance are needed to better understand transmission dynamics and human health risks.

Keywords: Amblyomma americanum; Heartland virus; lone star tick; thrombocytopenia; transmission.

Figure 1

Maximum-likelihood tree showing genetic relationships among the tick-borne, mosquito-borne, and sand-fly-borne phleboviruses. A maximum-likelihood phylogeny based on amino-acid sequences from the large (L) segment from representative strains was generated in PhyML using amino-acid sequences. Bootstraps are indicated on nodes, and tick, mosquito, and sand-fly vector associations are indicated by colored boxes. The scale bar represents the mean amino-acid substitutions per site. Accession numbers: Uukuniemi virus D10759; Precarious Point virus HM566181; Toscana virus FJ153281; Rift Valley fever virus JQ068144; Punta Toro virus KR912212; Lone Star virus NC 021242; Palma virus JQ956379; Bhanja virus JQ956376; Hunter Island virus KF848980; Malsoor virus KF186497; Heartland virus JX005846; severe fever with thrombocytopenia syndrome virus HM745930.

Figure 2

Heartland virus (HRTV) disease cases by state of residence and distribution of Amblyomma americanum. Map of the United States indicating states (Kansas, Oklahoma, Arkansas, Missouri, Tennessee, Kentucky, Indiana, Georgia, and South Carolina) with confirmed human HRTV cases (dark outline), as well as the county distribution of A. americanum representing established (dark-gray counties) and reported populations (light-gray counties) based on Reference [35].

Figure 3

Life stages of Amblyomma americanum. A. americanum is implicated as a probable vector of HRTV in North America based on repeated field isolations, vector competence, and catholic host-feeding behavior. White-tailed deer serve as hosts for all three A. americanum [36] life stages, but all stages can feed on humans. Adults feed principally on middle-to-large-sized mammals, while larvae and nymphs typically feed on ground-associated birds, middle-sized mammals, and occasionally, on small mammalian hosts.

Figure 4

Proposed transmission model for the Heartland virus. Proposed transmission cycle for HRTV between multiple life stages of A. americanum and various vertebrate hosts. (1) Adult A. americanum feed on white-tailed deer and become infected or were previously infected and possibly vertically pass HRTV infections to larvae. (2) Larvae feed on middle-sized mammalian hosts and possibly transmit HRTV or become infected while co-feeding on hosts with HRTV larvae or ticks of different life stages. (3) Larvae possibly transstadially passage HRTV to nymphal stage. (4) Nymphs and adult infected transstadially or by co-feeding possibly transmit HRTV to humans, middle- or large-sized mammalian hosts. (5) Co-feeding or transstadial transmission could occur from nymphal to adult stage. (6) Overwintering of infected nymphal or adult stages could occur with possible transmission in the spring.