Effectiveness of Seasonal Influenza Vaccinations Against Laboratory-Confirmed Influenza-Associated Infections Among Singapore Military Personnel in 2010–2013

Hin Peow Ho; Xiahong Zhao; Junxiong Pang; Mark I.-C. Chen; Vernon J. M. Lee; Li Wei Ang; Raymond V. Tzer Pin Lin; Christine Q. Gao; Li Yang Hsu; Alex R. Cook

Disclosures

Influenza Resp Viruses. 2014;8(5):557-566.

Abstract and Introduction

Abstract

Background Limited information is available about seasonal influenza vaccine effectiveness (VE) in tropical communities.

Objectives Virus subtype-specific VE was determined for all military service personnel in the recruit camp and three other non-recruit camp in Singapore's Armed Forces from 1 June 2009 to 30 June 2012.

Methods Consenting servicemen underwent nasal washes, which were tested with RT-PCR and subtyped. The test positive case and test negative control design was used to estimate the VE. To estimate the overall effect of the programme on new recruits, we used an ecological time series approach.

Results A total of 7016 consultations were collected. The crude estimates for the VE of the triavalent vaccine against both influenza A(H1N1)pdm09 and influenza B were 84% (95% CI 78–88%, 79–86%, respectively). Vaccine efficacy against influenza A(H3N2) was markedly lower (VE 33%, 95% CI −4% to 57%). An estimated 70% (RR = 0·30; 95% CI 0·11–0·84), 39% (RR = 0·61;0·25–1·43) and 75% (RR = 0·25; 95% CI 0·11–0·50) reduction in the risk of influenza A(H1N1)pdm09, influenza A(H3N2) and influenza B infections, respectively, in the recruit camp during the post-vaccination period compared with during the pre-vaccination period was observed.

Conclusions Overall, the blanket influenza vaccine programme in Singapore's Armed Forces has had a moderate to high degree of protection against influenza A(H1N1)pdm09 and influenza B, but not against influenza A(H3N2). Blanket influenza vaccination is recommended for all military personnel.

Introduction

Singapore is a city state that lies off the southern tip of the Malay Peninsula. Its location, <200 km from the equator, bestows a near constant year-round temperature and humidity and only moderately elevated rainfall during the monsoons. As a result, the timing of influenza outbreaks in Singapore is much less predictable than in temperate countries, with year-round potential for influenza transmission.

All male residents of Singapore undertake 2 years of national service on reaching adulthood and most serve in the Singapore Armed Forces (SAF). Servicemen initially undertake training at a dedicated camp ('the recruit camp' henceforth) off the main island of Singapore, Pulau Ujong. On completing training, they are posted to other camps, mostly on Pulau Ujong itself. Their service takes place in a semi-closed environment, and servicemen usually return to their families during the weekend, which may promote the transmission of infections between servicemen and the public. While on camp, soldiers live, work and socialise in close proximity, with potential for large outbreaks of respiratory infections such as influenza, akin to those observed in other closed or semi-closed populations, such as boarding schools or prisons.^[1]

The SAF implemented routine vaccination of new recruits with the H1N1-2009 vaccine when it became available at the end of 2009. Previous research found that this policy reduced H1N1-2009 disease burden among servicemen and hence recommended routine influenza vaccination of new recruits with the trivalent vaccine.^[2] Other settings have seen mixed findings on the effectiveness of non-pandemic or seasonal influenza vaccines. A study of seasonal influenza vaccine effectiveness (VE) among US military basic trainees in the 2005–2006 season showed that the VE against laboratory-confirmed influenza was 92%.^[3] Outside militaries, a 2011 systemic review showed pooled effectiveness of 59% for seasonal influenza by trivalent inactivated vaccine in the protection of adults aged 18–65 years.^[4] Other post-pandemic studies revealed an overall VE of 56% in the UK,^[5] 60% in the USA,^[6] 55% in Spain,^[7] and 30% against severe cases in high-risk individuals in France for H1N1-2009.^[8] Although these estimates indicate only moderate effectiveness on an individual basis, the protection afforded by herd immunity in a closed or semi-closed population, such as the SAF, may potentially result in greater effectiveness for a vaccine programme in reducing morbidity and absenteeism.

There is a paucity of studies that assess the effectiveness of blanket seasonal influenza vaccination over time in the same community. As a result, the expansion of the SAF vaccination programme to include all servicemen using the trivalent vaccine from 2011 onwards provides a unique opportunity to assess the effect of mass influenza vaccination to approximately half of an entire birth year cohort in a country. We estimated effectiveness of the 2011–2012 and 2012–2013 trivalent influenza vaccines in the Singapore military population using the standard test positive and test negative methodology, and the impact of the programme on reducing both influenza-related morbidity and overall febrile respiratory illness using a time series analysis approach.

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Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Descriptive characteristic of Singapore Armed Forces (SAF) servicemen with febrile respiratory illness (FRI) by age group, gender, camp, time period, vaccination status and subtype, 31 May 2009 to 30 June 2012 ( n = 7016)
Subjects characteristic	No. of samples	Influenza A(H1N1)pdm09		Influenza A(H3N2)		Influenza B
Subjects characteristic	No. of samples	No. of Positives (%)	P-value*	No. of Positives (%)	P-value*	No. of Positives (%)	P-value*
Age
15–19	326	3 (0·9)	<0·001	1 (0·3)	0·04	18 (5·5)	<0·001
20–24	5884	412 (7·0)		80 (1·4)		531 (9·0)
25–62	806	98 (12·2)		18 (2·2)		37 (4·6)
Gender
Male	7000	512 (7·3)	1	99 (1·4)	1	585 (8·4)
Female	16	1 (6·3)	1	0 (0·0)	1	1 (6·3)
Camp
Recruit Camp	5036	359 (7·1)	0·36	50 (1·0)	<0·001	511 (10·1)	<0·001
Other camps	1980	154 (7·8)	0·36	49 (2·5)	<0·001	75 (3·8)	<0·001
Time period
31 May 2009–30 November 2009	1336	294 (22·0)	<0·001	12 (0·9)	0·14	4 (0·3)	<0·001
1 December 2009–31 October 2010	2431	156 (6·4)		44 (1·8)		480 (19·7)
1 November 2010–30 September 2011	1784	56 (3·1)		23 (1·3)		42 (2·4)
1 October 2011–30 June 2012	1465	7 (0·5)		20 (1·4)		60 (4·1)
Monovalent vaccination
Yes	1415	43 (3·0)	<0·001	24 (1·7)	0·31	311 (22·0)	<0·001
No	5601	470 (8·4)	<0·001	75 (1·3)	0·31	275(4·9)	<0·001
Trivalent vaccination
Yes	2589	49 (1·9)	<0·001	28 (1·1)	0·08	56 (2·2)	<0·001
No	4427	464 (10·5)	<0·001	71 (1·6)	0·08	530 (12·0)	<0·001

*By Pearson's chi-square test, comparing proportions within groups.

Table 2. Crude and adjusted influenza monovalent and trivalent vaccine effectiveness by camp and subtype, 31 May 2009 to 30 June 2012 ( n = 7016)
Subtype	Influenza vaccine effectiveness (%) [95% confidence interval (CI)]
	Subjects with ≤14 days vaccination being classified as vaccination group (n = 7016)			Subjects with ≤14 days vaccination being classified as no vaccination group (n = 7016)
	Crude	Adjusted*		Crude	Adjusted*
	Crude	Recruit Camp	Other Camps	Crude	Recruit Camp	Other Camps
Monovalent Vaccine effectiveness
Influenza A(H1N1)pdm09, Period 2**	72 (59–81)	80 (70–87)	65 (−48 to 92)	94 (87–98)	97 (92–99)	63 (−57 to 91)
Trivalent Vaccine effectiveness
Influenza A(H1N1)pdm09, Period 3**	71 (49–84)	81 (64–90)	5 (−222 to 72)	69 (41–84)	76 (49–88)	30 (−162 to 81)
Influenza A(H1N1)pdm09, Period 4**	83 (23–96)	97 (49–100)	44 (−208 to 90)	46 (−144 to 88)	89 (−66 to 99)	24 (−331 to 87)
Influenza A(H3N2), Period 3**	60 (7–83)	−115 (−1748 to 75)	42 (−80 to 82)	59 (−5 to 84)	1 (−391 to 80)	56 (−56 to 88)
Influenza A(H3N2), Period 4**	49 (−55 to 83)	80 (16–95)	−73 (−127 to 78)	24 (−91 to 70)	71 (−23 to 93)	3 (−357 to 79)
Influenza B, Period 3**	86 (69–93)	90 (77–96)	69 (−163 to 96)	88 (66–96)	91 (71–97)	65 (−192 to 96)
Influenza B, Period 4**	70 (45–83)	71 (45–85)	65 (−39 to 91)	92 (84–96)	95 (88–98)	72 (−1·8 to 92)
Overall Influenza*, Period 3	77 (65–84)	83 (73–90)	39 (−34 to 72)	76 (61–85)	81 (66–89)	52 (−13 to 79)
Overall Influenza*, Period 4	69 (49–81)	77 (59–87)	34 (−83 to 76)	83 (73–89)	93 (86–97)	47 (−31 to 79)

*Variables being adjusted in all logistic regression models are camp group, vaccination period, vaccination history and interaction between vaccination history and camp group.
**Period 1 refers to the pre-vaccination period; period 2 refers to the period new recruits were given monovalent vaccination; period 3 refers to the period new recruits were given trivalent vaccination; and period 4 refers to the period all SAF servicemen received trivalent vaccination.
***The overall influenza includes influenza A(H1N1)pdm09, influenza A(H3N2) and influenza B.

Table 3. Relative risks for influenza infection from the ecological time series analysis, 31 May 2009 to 30 June 2012. Potential confounders included in all models are vaccination period, the number of cases in the recruit camp for the previous week before and after the vaccination programme and positive samples detected by the national surveillance programme
Model	Relative Risk [95% Confidence Interval (CI)]				No. of vaccinated positive cases in recruits during vaccination period (%)
Model	Vaccination Period versus No Vaccination Period*	AR Term in No Vaccination Period	AR Term in Vaccination Period	NPHL positive samples** (per 10 positive samples)	Subjects with ≤14 days vaccination being classified as vaccination group	Subjects with ≤14 days vaccination being classified as no vaccination group
Influenza A(H1N1)pdm09	0·30 (0·11–0·84)	1·01 (0·99–1·03)	1·16 (1·09–1·24)	1·05 (1·02–1·08)	53 (32·3)	17 (10·4)
Influenza A(H3N2)	0·61 (0·25–1·43)	1·29 (0·96–1·71)	2·25 (1·02–4·48)	1·45 (1·27–1·65)	10 (71·4)	6 (42·9)
Influenza B	0·25 (0·11–0·50)	1·06 (1·05–1·07)	1·19 (1·03–1·34)	1·31 (1·10–1·53)	43 (50·6)	8 (9·4)
FRI	0·84 (0·60–1·19)	1·00 (1·00–1·01)	1·01 (1·00–1·01)	1·01 (1·00–1·02)	3183 (75·2)	2390 (56·5)

AR, Autoregressive; NPHL, National public health laboratory; FRI, Febrile respiratory illness.
*No vaccination periods for each response variable are as follows: 31 May 2009 to 30 November 2009 for FRI and influenza A(H1N1)pdm09, 31 May 2009 to 31 October 2010 for influenza A(H3N2) and influenza B.
**NPHL data used for each response variable are as follows: total NPHL positive cases for FRI, A(H1N1)pdm09 NPHL positive cases for influenza A(H1N1)pdm09, A(H3N2) NPHL positive cases for influenza A(H3N2) and B NPHL positive cases for influenza B.