Severe fever and thrombocytopenia syndrome virus infection: Considerations for vaccine evaluation of a rare disease

Figures & data

Table 1. Mortality rates of SFTSV infection in Korea, 2013–2017

Year	# of reported cases ^1	# fatal cases ^2	Mortality rate (%)
2013	36	17	47.2
2014	55	16	29.1
2015	79	21	26.6
2016	165	19	11.5
2017	272	54	19.9
2018	259	N/A	N/A

¹ Yearly case data for SFTS infection are reported as part of the Korean CDC Weekly report at https://www.cdc.go.kr/CDC/eng/info/CdcKeDIDO.jsp?menuIds=HOME002-MNU0576-MNU0586

² Mortality data for SFTSV infection are reported by the Korean CDC at http://www.cdc.go.kr/npt/biz/npp/portal/nppPblctDtaMain.do. Mortality data for 2018 have not yet been reported by the Korean CDC.

Table 2. SFTS provincial case numbers and case rates for South Korea 2013–2018

Province	2013	2014	2015	2016	2017	2018	Total	Population (in millions)	Incidence per 100,000 population (2017)
Gyeonggi	0	8	7	28	56	47	146	12.24	0.45
Gangwon	3	4	15	29	39	35	125	1.57	2.48
Chungcheongbuk	0	2	0	11	12	12	37	1.58	0.76
Chungcheongnam	2	2	5	9	30	22	70	2.06	1.46
Jeollabuk	0	0	2	3	10	13	28	1.87	0.54
Jeollanam	5	1	9	9	18	16	58	1.90	0.95
Gyeongsangbuk	6	19	9	25	39	38	136	2.70	1.44
Gyeongsangnam	5	5	10	15	16	28	79	3.34	0.48
Jeju	6	7	9	8	21	15	66	0.6	3.50

Data as provided by the Korean CDC. Population data for 2018 were accessed at https://www.google.com/search?q=population+korea+provinces&ie=utf-8&oe=utf-8&client=firefox-b-1.

Table 3. SFTSV infection case numbers and case rates for high-incidence regions, South Korea 2013–2018

									Total		Total cases per 100,000 pop	Case rate per 100,000 pop^1
Country	Province	Region	2013	2014	2015	2016	2017	2018	2013–18	Population
Korea	Gyeonggi	Gapyeong-gun	0	0	4	10	7	5	26	63,157	41.2	7.9
		Namyangju-si	0	0	0	6	14	12	32	681,385	4.7	1.7
		Poncheon-si	0	1	0	2	9	3	15	151,495	9.9	2.0
	Gangwon	Wonju-si	0	0	5	5	3	8	21	343,367	6.1	2.3
		Inje-gun	0	2	3	4	6	5	20	32,179	62.2	15.6
		Chuncheon-si	2	1	0	7	12	5	27	280,582	9.6	1.8
	Gyeongsangbuk	Sangju-si	0	2	0	3	2	3	10	100,139	10.0	3.0
		Yeongju-si	0	0	0	0	3	5	8	107,136	7.5	4.7
		Uiseong-gun	1	0	0	0	0	5	6	52,929	11.3	9.5
		Pohang-si	2	2	0	1	5	5	15	510,401	2.9	1.0
	Jeju-do	Seogwipo-si	4	3	3	3	11	5	29	181,418	7.6	2.1
		Jeju-si	2	4	6	5	10	10	37	485,268	7.6	2.1

¹Case rates were calculated based on data from 2018.

Data as supplied by the Korean CDC.

Table 4. SFTSV infection case numbers and case rates, Japanese prefectures 2013–2018

							Total cases		Total cases per 100,000 pop	Case rate per 100,000 pop^a
Prefecture	2013	2014	2015	2016	2017	2018	2013–18	Population
Miyazaki	7	11	9	9	13	11	60	1,079,727	5.4	1.0
Kagoshima	5	4	6	4	11	9	39	1,613,969	2.4	0.6
Yamaguchi	3	4	6	4	12	8	37	1,368,495	2.6	0.6
Hiroshima	4	3	10	3	5	10	35	2,819,962	1.2	0.4
Kochi	3	11	3	7	5	5	34	705,880	4.7	0.7
Ehime	8	11	1	1	4	3	28	1,351,510	2.0	0.2
Nagasaki	5	2	2	2	11	4	26	1,339,438	1.9	0.3
Tokushima	2	7	3	8	4	1	26	736,475	3.3	0.1
Wakayama	0	2	1	5	3	5	16	934,051	1.7	0.5

^aCase rates were calculated based on data from 2018.

SFTS case data were provided from the following sources: Data for Korea was kindly provided by the Korean CDC. Case rates for Japan were collated from individual Infectious Diseases Weekly Reports for the following calendar years:

● 2018: https://www.niid.go.jp/niid/en/survaillance-data-table-english.html

● 2017: https://www.niid.go.jp/niid/en/survaillance-data-table-english/7756-idwr-sokuho-data-e-1752.html

● 2016: https://www.niid.go.jp/niid/en/survaillance-data-table-english/6999-idwr-sokuho-data-e-1652.html

● 2015: https://www.niid.go.jp/niid/en/survaillance-data-table-english/6199-idwr-sokuho-data-e-1553.html

● 2014: https://www.niid.go.jp/niid/en/survaillance-data-table-english/5251-idwr-sokuho-data-e-14-52.html

● 2013: https://www.niid.go.jp/niid/en/survaillance-data-table-english/4180-idwr-sokuho-data-e-13-52.html

Table 5. Sample size for SFTSV vaccine study in Korea

Category	Attack rate (per 100,000 population)	Vaccine effectiveness	Statistical Power	Estimated Sample size
Low	3.5	75%	80%	1,143,966
		90%	80%	730,536
Medium	22.5	75%	80%	177,930
		90%	80%	113,628
High	62.2	75%	80%	42,774
		90%	80%	41,102

Sample sizes are based a two-arm, placebo-controlled, double-blind study with 1:1 randomization. Korean estimates of SFTSV attack rates based on estimates derived from variable vaccine effectiveness, with a power of 80 at an α of 0.05. Attack rates are those from Jeju Province (low estimate) and Inje-gun region of Gangwon Province (high estimate).

Table 6. Assessment of SFTSV vaccine effectiveness using a case-control design as a function of time; vaccine efficacy of 90%

Region and incidence
Jeju Province	Non-vaccinated		Vaccinated
Time of follow-up	Person-years	Expected case #	Person-years	Expected case #
Vaccine efficacy >				0%	25%	50%	75%	90%
1 year	600,000	21	2,500	0.1	0.1	0	0	0
3 years	1,800,000	63	15,000	0.5	0.4	0.3	0.1	0.1
5 years	3,000,000	105	37,500	1.3	1.0	0.7	0.3	0.1
10 years	6,000,000	210	137,500	4.8	3.6	2.4	1.2	0.5
15 years	9,000,000	315	300,000	10.5	7.9	5.3	2.6*	1.1 ^φ
20 years	12,000,000	420	525,000	18.4	13.8	9.2*	4.6 ^φ	1.8^§
Inje-gun region	Non-vaccinated		Vaccinated
Time of follow-up	Person-years	Expected case #	Person-years	Expected case #
Vaccine efficacy >				0%	25%	50%	75%	90%
1 year	32,000	21.2	250	0.2	0.1	0.1	0	0
3 years	96,000	63.6	1500	1.0	0.7	0.5	0.2	0.1
5 years	160,000	105.9	3750	2.5	1.9	1.2	0.6	0.2
10 years	320,000	211.8	13,750	9.1	6.8	4.6	2.3*	0.9*
15 years	480,000	317.8	30,000	19.9	14.9	9.9*	5.0 ^φ	2.0^§
20 years	640,000	423.7	52,500	34.8	26.1	17.4 ^φ	8.7^§	3.5^§

For each region (Jeju Province or Inje-gun), the population represents an estimate of the entire population and is assumed to remain constant each year with population increases to match vaccine recipients. Actual person-years can be adjusted based on actuals once the SFTSV vaccine is licensed and enters into clinical use. For the vaccine group, person-years are cumulative such that if 2,500 persons are vaccinated in year 1, this group represents 7,500 person-years at the end of year 2. For Jeju Province, the population is estimated as 600,000 and for Inje-gun 32,000 for the purposes of the table. Expected cases are based on the reported incidence of infection as reported for 2017, 3.5 and 66.2 cases per 100,000 population, respectively.

Differences in the number of cases would that become statistically significant under these conditions are denoted: * p < 0.05, ^φ p < 0.01, ^§ p < 0.001. Comparisons were made using continuity-corrected Chi-Square analyses on the proportions of expected cases.