Serologic Evidence of Severe Fever with Thrombocytopenia Syndrome Virus and Related Viruses in Pakistan

We describe the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) and the association of antibody occurrence with location, sex, and age among the human population in Pakistan. Our results indicate substantial activity of SFTSV and SFTSV-related viruses in this country.

In the second step, we used a microneutralization test (MNT) assay to distinguish SFTSV-specific neutralizing antibodies from SFTSV-related viruses, as described elsewhere (6); we estimated SFTSV prevalence from ELISA and MNT results within 95% CIs. We performed statistical analysis of the data using the χ 2 test or Fisher exact test to explore the association of SFTSV with age, sex, and location. We performed the analysis in R version 3.5.1 with the Epicalc package version 2.15.1.0 (http://www.r-project.org).

Conclusions
This study highlights the activity of SFTSV and its substantial risks to the population in Pakistan. The observed high ELISA-based prevalence could be ascribed to the study population in this survey being livestock farmers, who could be more frequently exposed to tick vectors and livestock reservoirs. Higher estimates of SFTS prevalence in the Punjab province of Pakistan could be attributed to the high proximity of human and livestock populations in this region. Higher prevalence among women than among men was expected because livestock is mostly tended by female farmers.
In ELISA-based estimates of SFTSV in the human population reported from different areas of East Asian countries, seroprevalence has ranged from 0.23% to 9.17% in China (7), from 1.9% to 7.7% in Korea (8,9), and from 0.14% to 0.3% in Japan (10,11). In contrast to the findings from these reports (7-11), our study found a markedly high ELISA-based prevalence of SFTSV (46.7%) in Pakistan. The use of different SFTSV antibody detection methods may have led to the observed differences in results (11); nevertheless, results of the blind test using an immunofluorescence assay still suggested a high prevalence, such that 84.12% of the randomly selected ELISA-positive serum samples could react with the SFTSV antigen. Therefore, the low prevalence of neutralizing antibodies (2.5%) against SFTSV suggests the possibility of cocirculating antigenicity-related viruses that were not discernable in the indirect ELISA tests.
The genus Banyangvirus currently includes the Bhanja and SFTS/Heartland groups. The 5 viruses of the SFTS/Heartland group have a wide geographic distribution. SFTSV is found mostly in China, Japan, and South Korea (1); GTV in northwestern China (XJUAR) (4), Heartland virus in the United States (12); Hunter Island group virus in Australia (13); and Malsoor virus in India (14).
Similar to findings in our study, a high seroprevalence (19.8%) of GTV was detected among the local residents of Guertu County in Xinjiang, China; however, only 3 (0.65%) of the 465 serum samples had neutralizing antibodies against GTV (4). Antigenic cross-reactivity between SFTSV and GTV was suspected because cross-neutralization was observed in mouse serum (4). However, serologic investigation of other bunyaviruses is limited, and serotypes of the 2 viruses, as well as other related viruses in the SFTS/ Heartland group, remain unclear.
Our subsequent study found that a few serum samples exhibiting neutralization to SFTSV also exhibited cross-neutralization to GTV. All of these results indicate the presence in Pakistan of SFTSV and SFTSV-related viruses that might share antigenic similarity and could induce antibodies exhibiting cross-reactivity with each other. In addition, a recent study reported suspected Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 7, July 2020 1515 clinical SFTS cases in Pakistan; however, they were not confirmed using serologic or molecular tests (15). Our findings suggest the potential risk for infection from SFTSV and SFTSV-related viruses in Pakistan. Further work on the discovery, identification, and ecology of these viruses in ticks, animal hosts, and human patients is needed because the viruses pose potential threats to public health.

About the Author
Mr. Zohaib is a doctoral student at the Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. His major research interests include detection and characterization of zoonotic viruses.