Influenza vaccination of school teachers: A scoping review and an impact estimation.

INTRODUCTION: Influenza vaccination, besides protecting traditional risk groups, can protect employees and reduce illness-related absence, which is especially relevant in sectors with staff shortages. This study describes current knowledge of influenza vaccination in teachers and estimates its potential impact.
METHODS: We conducted a scoping review of the considerations for and impact of influenza vaccination of schoolteachers (grey and scientific literature up to 2020 March, complemented with interviews). We then estimated the potential impact of teacher vaccination in the Netherlands, with different scenarios of vaccine uptake for 3 influenza seasons (2016-2019). Using published data on multiple input parameters, we calculated potentially averted absenteeism notifications, averted absenteeism duration and averted doctor visits for influenza.
RESULTS: Only one scientific paper reported on impact; it showed lower absenteeism in vaccinated teachers, whereas more knowledge of vaccination impact was deemed crucial by 50% of interviewed experts. The impact for the Netherlands of a hypothetical 50% vaccine uptake was subsequently estimated: 74-293 potentially averted physician visits and 11,178-28,896 potentially averted days of influenza absenteeism (on ≈200,000 total teacher population). An estimated 12-32 vaccinations were required to prevent one teacher sick-leave notification, or 3.5-9.1 vaccinations to prevent one day of teacher absenteeism (2016-2019).
CONCLUSION: Scientific publications on influenza vaccination in teachers are few, while public interest has increased to reduce teacher shortages. However, school boards and public health experts indicate requiring knowledge of impact when considering this vaccination. Estimations of 3.5-9.1 vaccinated teachers preventing one day of influenza-related sick leave suggest a possible substantial vaccination impact on absenteeism. Financial incentives, more accessible on-site vaccinations at workplaces, or both, are expected to increase uptake, but more research is needed on teachers' views and vaccine uptake potential and its cost-effectiveness. Piloting free on-site influenza vaccination in several schools could provide further information on teacher participation.

Introduction

In the Netherlands and the European Union (EU), up to 2020, influenza infections reflected the highest burden of disease of all infectious diseases in disability-adjusted life years [1]. Annually, influenza infection causes many cases of influenza-like illness in the general population, hospitalisations and intensive care admissions [1]. It also contributes substantially to seasonal mortality rates [2]. The most important preventive measure is vaccination of risk groups with season-specific influenza vaccines [3, 4]. With influenza viruses constantly evolving (antigenic drift) [1] and waning antibody levels, a new vaccination campaign is needed annually [5]. The seasonal vaccine offers partial (roughly 30–50%) protection against medically attended, symptomatic infection if the match between the vaccine viruses and the circulating viruses is strong [6]; it provides less protection if circulating strains deviate from predicted.

Traditional risk groups targeted for influenza vaccination in many countries include the elderly (60+) and persons with underlying chronic conditions, because of their higher risk of influenza complications. In the Netherlands, this does not include teachers unless they are individually targeted because of fitting one of those traditional risk groups. In some countries, such as the United Kingdom (UK), healthy children are also eligible [1, 7]. The dual objective of such eligibility is to directly protect children while indirectly decreasing transmission to risk groups such as the elderly, since infants and schoolchildren are considered the drivers of influenza transmission in the wider community [1]. Influenza viruses are easily transmitted from person to person, particularly in crowded locations such as schools. European countries focus on risk groups, whereas in the United States (USA), routine annual influenza vaccination is recommended for all persons aged ≥6 months [6]. The Netherlands, as most European countries, also recommends annual vaccination of healthcare workers [1, 8], primarily aiming to protect their vulnerable patients.

Influenza vaccination may also protect employees in sectors other than health care and might reduce absenteeism due to influenza-associated illnesses [9]. This is especially relevant in sectors with staff shortages and where an influenza epidemic can have a profound impact on business continuity [9]. In the Netherlands, the healthcare sector and the educational system, particularly, the schoolteacher workforce, are especially vulnerable to disruption due to staff shortages [10-13].

Dutch media have reported on the lack of substitute teachers that has caused problems for schools in recent years [14, 15]. In the absence of national guidance on influenza vaccination in the educational system, some local companies and organisations encourage their staff to be vaccinated. For example, in Amsterdam, the public health service has offered free vaccination to schoolteachers since 2018/2019. However, little is known about this vaccination experience, its impact on teachers, or any similar considerations and policies in other municipalities. To our knowledge, no summary of available evidence on teacher vaccination is available.

Although Dutch media have recently reported on influenza vaccination of teachers as one way to decrease schoolteacher shortages, a comprehensive overview of literature is lacking. Therefore, we describe the current knowledge of teacher influenza vaccination using very broad input (scientific literature, grey literature, Dutch newspaper reports and information from key informants). Since knowledge of the impact of this vaccination in teacher populations is crucial for decision-making, but is lacking, we then estimated its potential impact.

Methods

We conducted a scoping review of the considerations for and impact of influenza vaccination of school teachers. We then estimated the potential impact of teacher vaccination in the Netherlands at different scenarios of vaccine uptake for three influenza seasons (2016–2019).

Scoping review

We conducted a scoping review of influenza vaccination of schoolteachers. The scoping review was based on the framework of Arksey and O’Malley [16]. We studied grey and scientific literature published up to March 2020. The literature was charted for study characteristics, details of vaccination implementation, vaccination uptake, teachers’ attitudes, and vaccination effect (impact).

Key information was extracted by one reviewer (S1 and S2 Files). This literature study was accompanied by interviews of 10 key informants in the two largest Dutch cities in 2020 (S3 File) and Dutch newspaper reports published from 2010 to 2019 (S4 File).

A scoping review was chosen, because our aim was to summarize the available evidence from both scientific and grey sources and to identify knowledge gaps in a specified research area where a comprehensive overview of literature is lacking [16, 17]. With a scoping review, we could address broader research questions and allow for redefinition of terms during the search process than we could with a systematic review. In a scoping review, authors do not typically assess the quality of the studies [17, 18], but we were able to exercise the option of including information from interviews with key informants.

Impact calculation

For multiple hypothetical vaccine uptake scenarios (2%, 10%, 25%, 50% and 70%), the potential impact of vaccinating schoolteachers for influenza was calculated by estimating the number of events the vaccine uptake would have averted (in seasons 2016/2017 to 2018/2019). We estimated the averted numbers of three different influenza-related events:

The potentially averted number of influenza absenteeism notifications among teachers (calculation in Fig 1).

Fig 1

Calculation of events, potentially averted events, and number needed to vaccinate to prevent one event [21, 26–34].

The potentially averted influenza absenteeism duration (i.e., the number of days of influenza absenteeism among teachers) (calculation in Fig 1).

The potentially averted number of general practitioner (GP) visits for influenza by teachers (calculation in Fig 1).

For each hypothetical uptake scenario, to calculate the potentially averted events, multiple season-specific input parameters (2016/2017, 2017/2018, 2018/2019) were collected from reports: the vaccine effectiveness, the size of the Dutch teacher population, the registered teacher self-reported influenza sick leave and duration, and the cumulative incidence of medically attended influenza-like illness in adults in primary care [19-34]. Because influenza sick leave and influenza-like illness can be caused by respiratory pathogens other than influenza, we further adjusted these rates by multiplying them by the proportion of specimens testing positive for influenza from sampled patients with influenza-like illness who visited a GP [32-34]. This proportion was from the total Dutch population, as teacher-specific data was not available. Separate season-specific parameters were used because the severity of influenza epidemics varies from year to year [3, 4]. Additionally, teacher populations, sick leave, and vaccine effectiveness can vary from year to year. We distinguished between primary and secondary school scenarios. In the Netherlands primary education covers ages 4–11 years (including kindergarten for 2 years and the following 6 years of classes, all in the same school), and secondary education covers ages 12 years and up (with a duration of 4 to 6 years of classes, depending on the school level).

We calculated the number of events potentially averted by influenza vaccination in the total teacher population of the Netherlands and separately for the two large cities: Amsterdam and Rotterdam.

Results

In total, 12 scientific articles and 23 grey publications were included in the final scoping review (Fig 2). S1 and S2 Files contain detailed descriptions, tables and summaries of Characteristics, Implementation details of vaccination, Vaccination uptake, Teachers’ attitudes, and Impact. In short, the 12 scientific articles were published between 2007 and 2019, mostly conducted in the USA, and were mostly questionnaire/survey-based. Only one scientific article reported the impact of influenza vaccination on teacher absenteeism [35]; the authors found that those who were vaccinated during a period of four months in 2007 had lower absenteeism than those who remained unvaccinated during that period (0.7% absenteeism vs 3.6%, p<0.001, on a study population size of 98, Gold Coast, Queensland, Australia), but they found no effect in 2009 when the vaccine viruses did not match the circulating viruses (see S1 File for additional results).

Fig 2

Flow diagram of publication selection process.

The 23 grey publications (published March 2007—February 2020) included little description of impact. News articles mentioned the offer of free influenza vaccination to reduce absenteeism [36], with one article stating that 75 is the number needed to vaccinate to prevent one case in healthy adults [37] (see additional results in S2 File).

Detailed results of interviews with 10 key informants are described in S3 File. Half of respondents expected the effectiveness of influenza vaccination for teachers to be low. The scientific evidence for the effect of vaccinating teachers was mentioned to be lacking but deemed crucial to be known, also by 50% of the respondents. The Dutch newspaper search resulted in 56 unique relevant articles (see S4 File for detailed results, Tables S4.2-S4.7 and Figures S4.1 and S4.2). The first newspaper article was published in February 2015, describing schools’ problems arranging for substitute teachers. The next reports followed two years later in a Belgian newspaper, and from February 2018 onwards, the number of reports in Dutch newspapers increased up to 22, 21 and 10 in season-years 2017/2018, 2018/2019 and 2019/2020, respectively. The overall sentiment of the articles was mainly positive (n = 30, 53.6%, excluding duplicates) regarding vaccinating schoolteachers for influenza, but 26.8% had no clear opinion, and 17.9% were negative (unknown: 1.8%).

Estimating influenza-related events

Estimated influenza absenteeism

In the three influenza seasons, teachers in primary education had a lower incidence of absenteeism notifications (range 1.0–1.2 per teacher per year) than those in secondary education (1.6–1.8 per teacher per year) [28] (Table 1). This data comprised overall absenteeism due to illness, but excluded absenteeism due to other reasons like maternity leave, study leave and emergency leave. Between 39.5% and 40.0% of the self-reported reasons for illness absenteeism was self-ascribed to influenza infection [29-31] (Table 1). The rate of positive test results for influenza virus obtained at GP visits for influenza-like illness was between 41% and 64%, depending on the season [21] (Table 1). Thus, the final calculation totaled 46,479–62,996 influenza absenteeism notifications per year in the total teacher population in the Netherlands (23–31% of total teacher population) (Table 2). Incidence of absenteeism notifications in Amsterdam was higher in both primary education (1.2–1.4 per teacher per year) and secondary education (1.9–2.2 per teacher per year) than it was nationally, while the incidence in Rotterdam was comparable with national numbers (1.0–1.2 per teacher per year in primary education and 1.6–1.7 per teacher per year in secondary education) (see S5 File, Tables S5.2 and S5.3 for all specific input parameters for Amsterdam and Rotterdam).

Table 1

Input parameters found for calculating the prevalence of teacher influenza events in the Netherlands nationally*.

INPUT PARAMETERS	2016/2017	2017/2018	2018/2019	2019/2020
Teacher population PE 1	127,088	127,006	128,275	129,022
Teacher population SE 2	75,585	75,973	75,694	75,284
Absenteeism notifications PE (per teacher per year) 3	1.2	1.0	1.1	n.a.
Absenteeism notifications SE (per teacher per year) 3	1.8	1.6	1.8	n.a.
Average duration per absenteeism PE (days per absence) 3	3.4	3.3	3.4	n.a.
Average duration per absenteeism SE (days per absence) 3	2.6	3.3	3.6	n.a.
Self-reported flu as reason for last absence (%)4, 5, 6	39.9	39.6	39.9	n.a.
Influenza-like illness GP visits (age 15–44) (per year per 10,000) ** 7	134	171	109	n.a.
Influenza-like illness GP visits (age 45–64) (per year per 10,000) ** 7	177	154	143	n.a.
Average influenza-like illness GP visits (age 15–64) (per year per 10,000) **	155.5	162.5	126	n.a.
Rate of specimens testing positive for influenza from influenza-like illness GP visits (age 15–64) 7	0.41	0.64	0.42	n.a.
I-MOVE+ pooled VE against H1N1 (age 15–64) 8	n.a.	50 (CI: 28 to 66)	49 (CI: 29 to 64)	n.a.
I-MOVE+ pooled VE against H3N2 (age 15–64) 8	33.6 (CI: 17.9 to 46.3)	33 (CI: -3 to 56)	-26 (CI: -66 to 4)	n.a.
I-MOVE+ pooled VE against B (age 15–64) 8	n.a.	21 (3 to 36)	n.a.	n.a.
Proportion H1N1/H3N2/B in Netherlands (all ages) 7 , 9	0.01/0.96/0.03	0.16/0.18/0.66	0.53/0.47/0.01	0.42/0.49/0.075
Weighted overall VE against influenza confirmed ILI for NL 7 , 8 , 9	32.3	27.8	13.75	n.a.

n.a. = not available (for VE: not available for influenza subtypes that hardly circulated in that year).

VE = vaccine effectiveness

PE = primary education

SE = secondary education

GP = general practitioner

* = for Amsterdam and Rotterdam specific input parameters, see S5 File Tables S5.2 and S5.3

** = in respiratory season (week 40 –week 20, with the average being the simple average of the incidence in those aged 15–44 and 45–64 years)

1 Report DUO: onderwijspersoneel PO in personen 2011–2019 [27];

2 Report DUO: onderwijspersoneel VO in personen 2011–2019 [26];

3 Report DUO: verzuimkengetallen 2016–2018 [28];

4, 5, 6 Report CBS: nationale enquête arbeidsomstandigheden 2016, 2017 and 2018 [29–31];

7Report RIVM: annual surveillance of influenza and other respiratory infections in the Netherlands [21].

8 I-MOVE end of season pooled influenza vaccine effectiveness report (2017 and 2018) [19, 20].

9 NIC, Nivel Nieuwsbrief influenza-surveillance 2016–2017, 2017–2018, 2018–2019 and 2019–2020 [22–25].

Table 2

Teacher population size and estimated† number of events per influenza-related event in teachers (absenteeism, physician visits).

	Netherlands		Amsterdam		Rotterdam
	min‡	max‡	min‡	max‡	min‡	max‡
Teacher population primary and secondary education **	202,673	203,969	9,357	9,428	7,627	7,710
Estimated notifications of influenza absenteeism (per year) *	46,479	62,996	2,520	3,542	1,713	2,356
Estimated total days of influenza absenteeism (per year) *	141,262	207,886	7,674	11,689	4,223	6,007
Estimated total influenza GP visits (per year)	1,079	2,111	50	97	40	78

* Teacher self-reported flu further adjusted for proportion of influenza positive specimens from adult influenza-like illness in patients in the national influenza surveillance.

** Total teacher population size available from ‘Dienst Uitvoering Onderwijs’ [26, 27].

† See S5 File for estimation details.

‡ Minimum and maximum value of the 3 estimations from the 3 years 2016/2017 to 2018/2019.

Estimated influenza absenteeism duration

Absenteeism duration is measured yearly in almost all Dutch teachers (coverage, 97–98% in primary education and 94–96% in secondary education 2016–2018). The average duration ranged from 20–22 days primary education and 12–14 days secondary education across the three seasons of 2016–2018) [28]. As this duration comprised overall sick leave, long-term sick leave skews this reported average upward. On the assumption that influenza infection causes only short-term sick leave, we adjusted these crude estimates by including only sick leave of ≤1 week’s duration with use of the reported survival tables. This adjustment resulted in a lower average duration of 3.3–3.4 days for primary education and 2.6–3.6 days for secondary education (Table 1). When sick leave of ≤2 weeks’ duration was included, the average was roughly 1.5 days higher. Separate survival tables were not reported for Amsterdam and Rotterdam. With their respective crude averages (Rotterdam: 17–18 days primary education and 9–10 days secondary education and Amsterdam: 18–22 days primary education, 13–14 days secondary education), we assumed the same underlying national duration distribution. We then calculated the two cities’ respective average short-term absenteeism (Rotterdam: 2.6–3.0 days primary education and 1.9–2.6 days secondary education and Amsterdam: 2.7–3.3 days primary education and 2.8–3.6 days secondary education) (Tables S5.2 and S5.3, S5 File). Multiplication of the estimated incidence of absenteeism notifications by the average days per sick leave gave an estimated total of 141,262–207,886 days of influenza-related sick leave per year in the teacher population in the Netherlands (Table 2).

Estimated total number of influenza-related GP visits

The incidence of GP visits for influenza-like illness in the working-age population per 10,000 inhabitants is calculated yearly [21]. During the study period, nationally, this incidence ranged between 109 and 171 per 10,000 inhabitants in groups aged 15–44 years and 45–64 years (groups roughly overlapped with work-force age; teacher-specific data were unavailable). We further adjusted this incidence for the rate of positive testing for influenza at GP visits [26, 27, 32–34]; this resulted in an annual estimated 1,079–2,111 influenza-related GP visits by teachers nationally, and an estimated 50–97 visits in Amsterdam, and 40–78 visits in Rotterdam (Tables S5.2 and S5.3, S5 File).

Estimating potentially averted influenza-related events

To calculate numbers of influenza-related events potentially averted by vaccination, we searched input parameters on vaccine effectiveness and set several hypothetical scenarios of vaccination uptake.

Vaccine effectiveness: Vaccine effectiveness in Europe is available from the I-MOVE project, pooling data from 11 countries (Table 1). The I-MOVE+ report of 2016–17 reported a vaccine effectiveness for only A(H3N2), as it was the main circulating strain. The vaccine effectiveness was 33.6% against laboratory-confirmed influenza subtype in the group aged 15–64 years [19]. The I-MOVE+ report of 2017–18 reported vaccine effectiveness’s for the group aged 15–64 of 50%, 33% and 21% against influenza subtypes A(H1N1)pdm09, A(H3N2) and influenza B, respectively [20]. For the 2018–19 season, interim I-MOVE results were used. A vaccine effectiveness of 49% and -26% against influenza subtypes A(H1N1) and A(H3N2), respectively, were reported in the report of surveillance of influenza in the Netherlands [21]. The National Influenza Centre (NIC) and the Netherlands Institute for Health Services Research (Nivel) reported proportions of influenza subtypes H1N1/H3N2/B in all ages of 0.01/0.96/0.03, 0.16/0.18/0.66, 0.53/0.47/0.01 and 0.42/0.49/0.075 for the seasons 2016/17, 2017/18, 2018/19 and 2019/20, respectively [22-25].

Vaccination uptake scenarios. Vaccination impact in hypothetical scenarios with a vaccination uptake of 2%, 10%, 25%, 50% and 70% was calculated with input of parameters reported for seasons 2016/2017-2018/2019. The two highest uptake scenarios were included, as this uptake was observed for one Dutch school board and reported in the USA [35, 38–47]. The lowest scenario was included, as this 2% uptake was observed for two years in Amsterdam [48, 49]. Importantly, the vaccination program was little known among many teachers (see interview results, S3 File).

Estimated number of influenza-related events averted

The estimated number of potentially averted events was calculated for the entire country, and separately for Amsterdam and Rotterdam (Table 3, and results per separate season given in S5 File, Tables S5.4-S5.6). In Amsterdam, a vaccination uptake of 2% in 2016/17 to 2018/19 would have averted 0–1 GP visits, 7–20 notifications of influenza absenteeism and 23–65 days of influenza absenteeism across those three seasons (Table 3). Had the vaccination uptake been 50%, it would have averted an estimated 3–14 GP visits, 185–492 notifications of influenza absenteeism and 585–1,625 days of influenza absenteeism across the three seasons (239–793 days in primary education; 346–832 days in secondary education). In Rotterdam, estimated potentially averted numbers would have been lower at 50% uptake, with 120–327 absenteeism notifications and 324–835 absent days, owing to the smaller teacher population and slightly lower sick leave numbers (Table 3). Nationally, at 2% vaccination uptake in 2018/2019, this estimate would have been 3–12 GP visits, 128–350 absenteeism notifications and 447–1,156 absent days; at 50% uptake, the estimate would have been 74–293 GP visits, 3,195–8,756 absenteeism notifications and 11,178–28,896 absent days (Table 3). Total averted influenza-related absenteeism days did not differ greatly by primary and secondary education (5,527–14,765 averted days in primary education; 5,651–14,131 averted days in secondary education) because the smaller secondary-teacher population was offset by higher absenteeism rates. Independent of location and event, a vaccination uptake of 2% was estimated to result in 0.3–0.6% prevented events, calculated by dividing the estimated number of averted events by the total estimated number of events. For a vaccination uptake of 50%, this number was estimated to increase to 6.9–16.1% prevented events (Table 4). Our results translate to 11.6–31.9 vaccinations required to prevent one teacher sick leave notification or 3.5–9.1 vaccinations to prevent one day of teacher absenteeism in the seasons 2016/2017 to 2018/2019 (Table 5).

Table 3

Estimated number of averted influenza events (NAE) in teachers by hypothetical vaccine uptake scenarios.

	NETHERLANDS		AMSTERDAM		ROTTERDAM
	Estimated NAE (notifications of influenza absenteeism)
Hypothetical vaccination uptake scenario	min	max	min	max	min	max
2%	304	735	18	40	11	27
10%	1522	3677	88	198	57	135
25%	3804	9191	220	496	143	337
50%	7608	18383	439	991	286	674
70%	10651	25736	615	1388	400	943
	Estimated NAE (total days of influenza absenteeism)
Hypothetical vaccination uptake scenario	min	max	min	max	min	max
2%	5499	11933	278	636	164	360
10%	27496	59663	1390	3180	818	1802
25%	68739	149159	3476	7950	2044	4504
50%	137478	298317	6952	15900	4088	9009
70%	192470	417644	9733	22260	5723	12612
	Estimated NAE (influenza GP visits)
Hypothetical vaccination uptake scenario	min	max	min	max	min	max
2%	3	12	0	1	0	0
10%	15	59	1	3	1	2
25%	37	147	2	7	1	5
50%	74	293	3	14	3	11
70%	104	411	5	19	4	15

Min/max: the lowest (minimum) and highest (maximum) estimate observed within the 3 calculated seasons (2016/2017-2018/2019).

Table 4

Prevented proportion* of all influenza events in teachers by different vaccine uptake scenarios.

Hypothetical vaccination uptake scenario	Prevented proportion
	min (%)	min (%)
2%	0,3	0,6
10%	1,4	3,2
25%	3,4	8,1
50%	6,9	16,1
70%	9,6	22,6

* Estimated number of averted events divided by total estimated number of events. These are independent of location and type of influenza event (absenteeism notifications, or duration, or GP visits).

Min/max: the lowest (minimum) and highest (maximum) estimate observed within the 3 calculated seasons (2016/2017-2018/2019).

Table 5

Number needed to vaccinate to prevent one event.

	NETHERLANDS		AMSTERDAM		ROTTERDAM
	min	max	min	max	min	max
Number needed to vaccinate to prevent one notification influenza absenteeism	11.6	31.9	9.5	25.5	11.5	31.4
Number needed to vaccinate to prevent one working day lost due to influenza absenteeism	3.5	9.1	2.9	8.0	4.5	11.6
Number needed to vaccinate to prevent one influenza GP visit	346	1374	346	1374	346	1374

Min/max: the lowest (minimum) and highest (maximum) estimate observed within the 3 calculated seasons (2016/2017-2018/2019).

Discussion

Our study shows a paucity of scientific publications on teacher influenza vaccination, while public interest on the topic has increased. If vaccine uptake were to be moderate to high, impact on sick leave could be considerable.

Of 12 scientific papers, only a study in Australia reported the impact of vaccinating school teachers for influenza; vaccinated teachers had lower rates of absenteeism than those who were unvaccinated. The other 11 papers mainly assessed teachers attitudes and uptake, mostly in the USA. Grey literature showed that a few European countries nationally recommend influenza vaccination for teachers. In the Netherlands, no municipality, except Amsterdam in 2018 and 2019, was found to offer free influenza vaccination to teachers. However, multiple Dutch school boards do offer vaccination to their personnel, according to key informants and some newspaper articles. The main motivation for the offer was a reduction in absenteeism, but vaccine uptake levels were unreported. Unfortunately, details on how and where vaccinations were provided were either not known or not given. From February 2018, amidst a heavy influenza season, Dutch newspaper reporting on this topic increased; often reporting a positive attitude towards vaccination. However, the vaccination campaign among teachers in Amsterdam resulted in a vaccination uptake of only 2%, which was lower than expected. Reportedly, this low result could have occurred because the plans for vaccine administration were made hastily. Vaccinations were offered on only 2 evenings at one health centre, and the reach of the teacher population was limited. Interviewees expected that if communication and vaccination accessibility were to improve that vaccination uptake by teachers would increase. However it is unclear what the uptake would have been if Amsterdam had reached out to all teachers directly or had provided at-school vaccination.

Some key informants viewed financial incentives as unnecessary or undesirable, but these incentives were reported in grey literature to increase vaccination uptake. While vaccination uptake and its predictors have been studied in in a different sector (health care workers [50, 51]), Dutch teachers’ knowledge of influenza vaccination and their attitudes regarding it are unknown. Future research could specifically address teachers through survey or interviews to understand their attitudes, concerns and practical barriers regarding influenza vaccination. Additionally, a pilot study offering free influenza vaccination on location to pre-informed teachers in several schools could provide actual teacher participation rates in an easily accessible setting and might provide key lessons for new or different vaccination campaigns. Many key informants expressed that they needed to know the potential impact of teacher influenza vaccination Future research should also focus on estimating the effect on sick leave of vaccinating teachers. Our impact calculations provide an initial estimate of influenza sick leave that might be averted by vaccinating the teacher population. The reduction in sick leave could be considerable with a moderate to high vaccination uptake. Future research should additionally focus on the cost-effectiveness of teacher vaccination both for schools and for public health generally. Ideally it would also consider the potential effects of easier accessibility and financial incentives on the uptake.

In the Netherlands, local teacher shortages were the main motivation for offering free influenza vaccination to school teachers (in Amsterdam, and by few school boards elsewhere). The educational sector showed a higher-than-average absenteeism, with an increasing percentage due to influenza infection [29-31]. The largest teacher shortages were in the western part of the Netherlands [10, 11], the same region with the largest number of newspaper articles about teacher influenza vaccination. Teacher shortages have been increasing, and the largest increase shown in online vacancies was in 2017/2018, a year with a very severe influenza season [52]. The number of vacancies increased by 50% compared to the previous year for personnel in primary education and by almost 25% in all education sectors combined [10]. In 2019, teacher shortages were 3.4%, 2.7% and 2.0% in the large cities of Amsterdam, Rotterdam and The Hague, respectively. In 2020 these numbers were expected to reach 8.4%, 6.6% and 4.7%, respectively [11]. In these three cities, requests have come from either the council’s education department (Amsterdam) or a political party (Rotterdam and The Hague) to set up a vaccination programme for school teachers or to investigate the feasibility of such a plan. Dutch health care workers [51, 52] are offered free influenza vaccination to protect their vulnerable patients. But decreased absenteeism and uninterrupted care are considered additional benefits [53]. This outcome could be similar in the education sector for which potential uptake and predictors are not yet known.

A Cochrane review by Demicheli 2014 found that in healthy adults (not specifically school teachers and staff), at least 71 people required vaccination to prevent one laboratory-confirmed case of influenza (CI: 64 to 80) [54]. However, many influenza infections are usually not laboratory-confirmed. Their number is more optimistic than our estimate of 346–1374 vaccinations to prevent one teacher visit to a GP in the Netherlands. These are specifically visits for influenza-related illness, which we assume to be a relatively similar event to the laboratory confirmed cases in Demichelli’s review. Laboratory testing and physician consultation might occur relatively late in the disease process. At the earlier disease stage of taking sick leave for influenza, our results indicate that only 3.5–9.1 vaccinated teachers were needed to prevent 1 day of teacher influenza sick leave. These are relevant results, as there is uncertainty about the effect of vaccines on working days lost [5]. Our relatively high estimates of potentially averted absenteeism in teachers may be likely, given the conclusion of Nichol et al (1995). They reported that immunization decreased absenteeism from work due to upper respiratory illness by 43% and absenteeism due to all illnesses by 36% in healthy, working adults [55]. Saxen et al (1999) studied the effect of influenza vaccination in health care providers working in paediatric settings. They found a reduction of 28% in absenteeism related to respiratory infections [56]. Another review study of health care workers concluded that absenteeism was less frequent and shorter in those vaccinated, but the magnitude of this reduction was unavailable [57].

In school children, influenza vaccination showed a positive effect on overall influenza morbidity, not only in schools [58] but also in the community [43, 59]. For the 2009 H1N1 influenza pandemic, it was found that vaccinating school children decreased absenteeism of both teachers and students [60].

Whether teachers have a greater risk of influenza infection is not clear. Teachers possibly are at higher risk of head/chest colds compared to other workers [61], but these may not be caused solely by influenza viruses. In contrast, Elizondo-Montemayor, et al. showed the prevalence of influenza A(H1N1pmd09) antibodies did not differ between school teachers (elementary and middle school) and the general population. The antibody prevalence was even lower in high school teachers than in the general population [62].

Calculating the potential impact of vaccination comes with some difficulties. One pitfall of our impact calculations is that we did not calculate additional effects. For instance, one report showed that 77% of the school employees with symptoms of influenza-like-illness did not report being sick and worked while ill [39]. Vaccination would also reduce this phenomenon, but we could not calculate this potential impact due to lack of Dutch data. Additionally, we did not account for the herd immunity that might occur with higher vaccination uptake, resulting in a larger impact than we estimated. For Amsterdam, we assumed that none of the teachers, other than those vaccinated at the public health service, had received influenza vaccination from their GP in that year within the national vaccination programme for risk groups. But, some teachers probably had received vaccination from their GP because of age (60+) or underlying medical conditions (within the general immunization programme). The actually registered sick leave that we used as input parameter would have been higher had they not been vaccinated within the general immunization programme. Therefore, we expect that we have underestimated, rather than overestimated, impact of vaccinating teachers. The vaccination campaign in Amsterdam seemed little known among teachers, and vaccination uptake was expected to be higher if all teachers had been informed. In health care workers, easier access to vaccination and education programmes on influenza vaccination were reported to increase vaccination uptake [63]. Both might also increase the vaccination uptake in teachers. Higher vaccination uptake would result in a higher estimated impact. To avoid overestimation of the number of days of sick leave due to influenza infection, we assumed influenza caused only short-term sick leave of ≤7 days. Thus we had included only short sick leave reported by teachers as an input parameter in our estimation. This might have resulted in an underestimation of impact, as influenza can also cause sick leave >7 days. However, only 4–5% of all sick leave was reported as lasting 8–14 days. We performed straightforward impact calculations. Future study could incorporate the scenarios of uncertainty in the various input data and thus improve the estimates by providing a range for the expected impact. The proportion of teachers’ self-reported cases of influenza that were actually caused by the influenza virus needs investigation. For lack of data, we assumed it was the same as the proportion of visits to GP’s for influenza-like illness that were confirmed as caused by the influenza virus (known for the general population, not for teachers specifically).

The current COVID-19 pandemic could lead to increased attention focused on seasonal influenza vaccination in teachers. The influenza H1N1 pandemic in 2009 also resulted in multiple countries adding risk groups to their national recommendations for the influenza vaccination [64] and increased seasonal influenza vaccine uptake in the 2009/2010 season [65]. Additionally, increasing seasonal influenza vaccine uptake to reduce the burden of the disease is a key focus of the EU and World Health Organization in preparation for COVID-19 resurgences [66]. Also, the management of pressure in the education sector that has been burdened already with staff shortages may receive increasing attention.

In conclusion, international scientific literature on influenza vaccination of teachers remains sparse and vaccination of this group is not nationally advised in most countries. However, Dutch media attention is growing, sparked by teacher shortages in recent years. The impact of vaccinating teachers has been particularly understudied. This is the case despite some key experts and media have reported that any school board or other entity that is considering offering influenza vaccination to teachers needs to understand the impact of the vaccination. Our estimates showed that vaccinating teachers against influenza might be associated with a substantial decrease of sick leave days due to that viral infection. Teacher surveys, in-depth cost-effectiveness studies and a pilot at-school influenza vaccination programme could provide critical information about teacher vaccination.

Scientific literature review.

(DOCX)

Click here for additional data file.

Grey literature review.

(DOCX)

Click here for additional data file.

Interviews.

(DOCX)

Click here for additional data file.

Newspaper monitoring.

(DOCX)

Click here for additional data file.

Impact calculations.

(DOCX)

Click here for additional data file.

Prisma checklist scoping review.

(DOCX)

Click here for additional data file.

15 Mar 2021

PONE-D-20-40234

Influenza vaccination of school teachers: a scoping review and an impact estimation

PLOS ONE

Dear Dr. Huiberts,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by 8th April 2021. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Shinya Tsuzuki, MD, MSc

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

3. Our staff editors have determined that your manuscript is likely within the scope of our Call for Papers on Influenza. This editorial initiative is headed by PLOS ONE Guest Editors Dr. Meagan Deming and Dr. Deshayne Fell. The Collection encompasses research on influenza prevention on every level, including in vitro, translational, behavioral, and clinical studies; disease and immunity modelling; as well as new approaches to influenza prevention. Additional information can be found on our announcement page: https://collections.plos.org/call-for-papers/influenza/.

Currently, your manuscript is included in the group of papers being considered for this call. Please note that being considered for the Collection does not require additional peer review beyond the journal’s standard process and will not delay the publication of your manuscript if it is accepted by PLOS ONE. We would greatly appreciate your confirmation that you would like your manuscript to be considered for this Collection by indicating this in your next cover letter. If you would prefer to remove your manuscript from collection consideration, please specify this in your cover letter.

4. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified whether consent was informed.

5. We note that Figure 3 in your manuscript and Figure 2 in S4 file contain map images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software (Google Maps, Street View, and Earth). For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright.

We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:

(1) You may seek permission from the original copyright holder of Figure 3 and Figure 2 in S4 file to publish the content specifically under the CC BY 4.0 license.

We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:

“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”

Please upload the completed Content Permission Form or other proof of granted permissions as an "Other" file with your submission.

In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].”

(2) If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.

The following resources for replacing copyrighted map figures may be helpful:

USGS National Map Viewer (public domain): http://viewer.nationalmap.gov/viewer/

The Gateway to Astronaut Photography of Earth (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/

Maps at the CIA (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.html

NASA Earth Observatory (public domain): http://earthobservatory.nasa.gov/

Landsat: http://landsat.visibleearth.nasa.gov/

USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://eros.usgs.gov/#

Natural Earth (public domain): http://www.naturalearthdata.com/

Additional Editor Comments:

In this time, the decisions made by reviewers were split, but I believe that the points both reviewers mentioned can be addressed by appropriate revision. At present the manuscript includes too many kind of methodologies, and as a result, it becomes distracted to some extent. The scope of the manuscript should be clearer through its revision process.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript presents the results of a scoping review and impact assessment of influenza vaccination of teachers in the Netherlands. Given the current discussion around COVID-19 vaccination of teachers and safely opening schools it is a highly relevant research question. Overall the article is clearly written and obviously represents a massive amount of work. However, I think there is too much information in this manuscript for one scientific article. I would recommend that the authors focus on the impact assessment, as the results of the scoping review (namely, there hasn't been much done in this field) are not particularly surprising. I suggest moving the scoping review methods and much of the results to a supplement (or splitting the manuscript into separate articles). I have attempted to provide some detailed comments by manuscript section, but these comments would likely be much more helpful to the authors once there has been a decision on how to proceed in regards to splitting of changing the focus of the current manuscript.

Introduction

Page 7 Line 102 - It is not universally true that there is no protection from year to the next. In fact, early life influenza infection has been shown to influenza susceptibility to later life infection This is particularly for H1N1pdm09 which has seen relatively little antigenic drift since it was established as a seasonal virus. Similarly, waning antibody level is another reason for annual vaccination campaigns.

Be specific about the protection afforded by seasonal influenza vaccines. The 30-50% number reported by CDC is against medically attended, symptomatic infection.

Page 7 line 117 - this phrasing is a little awkward. I would suggest saying that vaccination is associated with a reduction in absenteeism due to influenza associated illnesses.

Methods

The search strategy was clearly described. But why was January 2000 selected as a start date? Is this tied to Dutch vaccine recommendations or other criteria? If there is no rationale for the time restriction I would open it up to include any dates (with the expectation that very few studies were done prior to 2000). Of note, none of the included articles were published before 2007, this tracks with US vaccine recommendations which were expanded in the 2000s and early 2010s.

Results

Line 220 - Include reasons why scientific articles and grey publications were excluded - are the detailed descriptions of the 12 or the 15

Line 367 - You say absenteeism was reduced by too little to justify continuing the program according to a newspaper article. Was the actual reduction noted?

How was tone of the article (e.g. positive, indifferent) determined?

Line 387 - "we adjusted this number" - How was this adjustment done? What assumptions were made?

Discussion

Much of the first paragraphs in the discussion are repetition of what was presented in the scoping review section of the results.

Estimates of cases averted and absenteeism have been in the US, but don't seem to be mentioned in the discussion.

Overall

In my opinion, the scientific value of this paper is really in the impact assessment. I would reframe the narrative throughout to focus on that, minimizing the scoping review. This would mean a very brief summary of the scoping review methods and results, with most of the detail moved to the supplementary materials. In contrast I think much more detail is needed in the methods section for the impact assessment. Similarly the results section should focus primarily on the impact assessment instead of burying that material at the end after a detailed descriptions of the review.

Reviewer #2: Review

In this study, the authors conducted a comprehensive review on flu vaccination administered to school teachers and evaluated its requirements and rationale. I consider that this study’s objectives were (at least partially) achieved by using a combination approach of scoping review, interview, and impact estimation. However, this study is very complex because many issues and study methods are handled in the same paper. I believe this paper is worth publishing. However, some attempts to improve the readability are needed.

1. In my opinion, scoping review, interview (qualitative study), newspaper search, and impact estimation (modeling) seem different. Since the study consisted of synthesizing these four different studies, this manuscript looks like a policy document rather than an academic write-up. To clarify the scope of each study part, I suggest that the authors explain the aims and reasons for which this method was selected in every part.

2. In addition, the deductive theory flow in this study is as follows: 1. There is a lack of school teachers in Netherlands –> 2. The flu outbreaks worsen this situation –> 3. vaccine could save this situation –> 4. Currently, vaccination is not satisfactorily performed -> 5. So how can we do it? I consider this flow to be inconsistent in this manuscript in each part, leading to a decrease in readability. Therefore, I believe that being conscious of this flow can help readability.

3. Did the author know the low vaccine prevalence in Amsterdam before this survey was performed? If the authors knew this fact before the survey, I think they should mention the low vaccine prevalence in the Introduction section. This is because the low vaccine prevalence could explain the reason for this study and its rationale naturally.

4. In the Introduction section, the authors mentioned “overviewing any aspect vaccinating teachers against influenza,” however, the aim of the scoping review is identifying “gaps” between existing evidence and required evidence to state the specific purpose of scoping. Therefore, the authors should first define the aim of this scoping review. In this study, I understand that this scoping review aimed to collect evidence on the spread of flu vaccinations among school teachers.

5. Regarding this scoping review, did the authors identify regions with inadequate vaccination evidence based on the author’s purpose? This seems to be mentioned in the Conclusion section, although I could not find it in the main text.

6. The review of newspapers did not have an impact on the integrity of this study. Additionally, I do not know the scientific validity of these methods. Therefore, it may be better to remove this part from this study.

7. In the impact estimation part, statements that should be written in the Methods section are frequently seen in the Results section (model selection, way of adjustment, etc.). Please consider ameliorating this structure.

8. The conclusion is unclear. It could be understandable if the objectives of each part of this study are made intelligible.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Yoshiki Kusama

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

23 Mar 2022

We thank the reviewers for their comments and suggestions. We believe they have greatly contributed to improving the quality and clarity of the work. Below, we provide a point by point response to all their points and to the additional PLOS ONE requirements.

PloS One additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Reply: Thank you, we have checked the file names and all other PLOS ONE requirements.

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

REPLY: Checking the provided PLOS ONE link we have now changed this. We have made the data available in the manuscript, the anonimized excerpts of the interviews are in supplement S3 (pages 10-18).

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

REPLY: We checked our information letter and our consent form and we have now made the data available in the manuscript, see also point b below.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

REPLY: We have added the anonymized excerpts of the interviews in supplementary S3 (pages 10-18).

We will update your Data Availability statement on your behalf to reflect the information you provide.

3. Our staff editors have determined that your manuscript is likely within the scope of our Call for Papers on Influenza. This editorial initiative is headed by PLOS ONE Guest Editors Dr. Meagan Deming and Dr. Deshayne Fell. The Collection encompasses research on influenza prevention on every level, including in vitro, translational, behavioral, and clinical studies; disease and immunity modelling; as well as new approaches to influenza prevention. Additional information can be found on our announcement page: https://collections.plos.org/call-for-papers/influenza/.

Currently, your manuscript is included in the group of papers being considered for this call. Please note that being considered for the Collection does not require additional peer review beyond the journal’s standard process and will not delay the publication of your manuscript if it is accepted by PLOS ONE. We would greatly appreciate your confirmation that you would like your manuscript to be considered for this Collection by indicating this in your next cover letter. If you would prefer to remove your manuscript from collection consideration, please specify this in your cover letter.

REPLY: we are certainly happy for publication within, or outside of this call, as PLOS ONE would wish.

4. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified whether consent was informed.

REPLY: We have added additional detail in the online submission form as well as to the methods section. For this we added the following sentences to supplement S3:

‘Potential participants were approached by email and they received a letter asking whether they would agree to participate. The letter explained the research aims, interview procedures, and privacy matters (de-identification of transcripts). Written and oral consent was obtained from each consenting interviewee. The consent form included queries on whether the interviewee had read the information letter and whether all their queries and concerns had been addressed satisfactorily. Ethical approval was not required for this study according to Dutch legislation, as it concerned a once only interview.’ (Supplement S3, page 1-2, lines 26-38)

5. We note that Figure 3 in your manuscript and Figure 2 in S4 file contain map images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software (Google Maps, Street View, and Earth). For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright.

REPLY: We have now produced these map images using the free R statistical package, which is without copyright [R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/]. The source data on province areas as available from Statistics Netherlands (CBS) and the Dutch land registry (Kadaster). Metadata are freely downloadable without copyright from the Dutch National Geo Registry: https://www.nationaalgeoregister.nl/geonetwork/srv/dut/catalog.search#/metadata/effe1ab0-073d-437c-af13-df5c5e07d6cd?tab=general).

To clarify these two sources for readers we have added the following subscript below the figure: ‘* province: data on province areas as available from Statistics Netherlands (CBS) and the Dutch land registry (Kadaster). Metadata are freely downloadable without copyright from the Dutch National Geo Registry: https://www.nationaalgeoregister.nl/geonetwork/srv/dut/catalog.search#/metadata/effe1ab0-073d-437c-af13-df5c5e07d6cd?tab=general). The figure is made using statistical software R [R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/]’.

Due to the reviewers other request on page 4 to focus more on the impact estimates and thus move much other text to the supplements, the map image of figure three has been removed from the main manuscript, and can be found in the supplement S4 (as figure S4.2).

Additional Editor Comments:

In this time, the decisions made by reviewers were split, but I believe that the points both reviewers mentioned can be addressed by appropriate revision. At present the manuscript includes too many kind of methodologies, and as a result, it becomes distracted to some extent. The scope of the manuscript should be clearer through its revision process.

REPLY: We thank PLOS ONE for the thorough review. As both reviewers mention that the manuscript includes many methodologies, we followed the advice of both reviewers to move most parts of the scoping review to the supplements and to focus the main document more on the estimated impact sections. As suggested by the reviewers, a very short summary of methods and the main findings of the scoping review now remain in the main text, with reference to all scoping review details in supplements S1-S4. Then, in the manuscript we further elaborated on the methods and results of the impact estimates. This indeed clarifies the scope of the manuscript which is summarized in the abstract as follows: ‘This study describes current knowledge of influenza vaccination in teachers and estimates its potential impact’.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

REPLY: To better clarify the scientific research we have expanded the description of the methods and results section of the impact estimation (as was also suggested by both reviewers in their separate comments) (page 9-10, lines 144-174 and page 11-19, lines 208-348). We have now also included an additional figure explaining the calculations (figure 2).

________________________________________

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

REPLY: Thank you.

________________________________________

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

REPLY: Thank you.

________________________________________

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

REPLY: The manuscript has now been edited by a professional English language editor (S. Ebeling, freelance editor who has previously worked for The New England Journal of Medicine)

________________________________________

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript presents the results of a scoping review and impact assessment of influenza vaccination of teachers in the Netherlands. Given the current discussion around COVID-19 vaccination of teachers and safely opening schools it is a highly relevant research question. Overall the article is clearly written and obviously represents a massive amount of work. However, I think there is too much information in this manuscript for one scientific article. I would recommend that the authors focus on the impact assessment, as the results of the scoping review (namely, there hasn't been much done in this field) are not particularly surprising. I suggest moving the scoping review methods and much of the results to a supplement (or splitting the manuscript into separate articles). I have attempted to provide some detailed comments by manuscript section, but these comments would likely be much more helpful to the authors once there has been a decision on how to proceed in regards to splitting or changing the focus of the current manuscript.

REPLY: We appreciate the reviewer’s compliments regarding the relevance of the research question and the amount of work involved. We followed his/her advice to focus more on the impact assessment and to move much of the scoping review methods and results to the supplements (see supplements S1-S4). This is also in line with the same suggestion done by reviewer 2. A brief summary of the scoping review methods and results remain in the main manuscript. And we now elaborated much more on the methods and results section of the impact estimation. We also included an additional figure explaining the impact calculations (figure 2).

Introduction

Page 7 Line 102 - It is not universally true that there is no protection from year to the next. In fact, early life influenza infection has been shown to influenza susceptibility to later life infection This is particularly for H1N1pdm09 which has seen relatively little antigenic drift since it was established as a seasonal virus. Similarly, waning antibody level is another reason for annual vaccination campaigns.

REPLY: We agree with the reviewer that this is not universally true. We have removed the section about a lack of year to year protection and we changed the sentence to:

‘With influenza viruses constantly evolving (antigenic drift) [1] and waning antibody levels, a new vaccination campaign is needed annually [5].’ (page 6 lines 86-87)

Be specific about the protection afforded by seasonal influenza vaccines. The 30-50% number reported by CDC is against medically attended, symptomatic infection.

REPLY: Thank you for noticing this omission, we have added that this is indeed against medically attended infection:

‘The seasonal vaccine offers partial (roughly 30-50%) protection against medically attended, symptomatic infection if the match between the vaccine viruses and the circulating viruses is strong [6]; it provides less protection if circulating strains deviate from predicted.’ (page 6 lines 87-90)

Page 7 line 117 - this phrasing is a little awkward. I would suggest saying that vaccination is associated with a reduction in absenteeism due to influenza associated illnesses.

REPLY: We agree that the phrasing was awkward. We have now rephrased to:

‘Influenza vaccination may also protect employees in sectors other than health care and might reduce absenteeism due to influenza-associated illnesses [9].’ (page 6 lines 103-104)

Methods

The search strategy was clearly described. But why was January 2000 selected as a start date? Is this tied to Dutch vaccine recommendations or other criteria? If there is no rationale for the time restriction I would open it up to include any dates (with the expectation that very few studies were done prior to 2000). Of note, none of the included articles were published before 2007, this tracks with US vaccine recommendations which were expanded in the 2000s and early 2010s.

REPLY: The selected period (2000-2020) was not tied to any policy or recommendations. As suggested by the reviewer we have opened up the time restriction to include any dates prior to 2000. This provided two additional scientific papers which after screening were not relevant (they were not about influenza vaccination in teachers). We adjusted the selected search period in the methods section (Page 8, S1, S2) and we adjusted figure 2 to reflect this search strategy change.

Results

Line 220 - Include reasons why scientific articles and grey publications were excluded - are the detailed descriptions of the 12 or the 15

REPLY: We agree with the reviewer that we had omitted this information. We have added the following text to the methods of the scientific and grey literature search:

‘Publications were excluded if they were not about influenza vaccination or not about teachers’. (supplement S1, page 1 lines 20-21, and supplement S2, page 1 lines 25-26)

Line 367 - You say absenteeism was reduced by too little to justify continuing the program according to a newspaper article. Was the actual reduction noted?

REPLY: Unfortunately the newspaper item did not provide the actual reduction, which we now added to the sentence as follows: ‘The latter stopped offering teacher vaccination as absenteeism reduced too little. However, details on the magnitude of reduction and how and where vaccination was offered by these boards are not given.’ (supplement S4 page 2 lines 77-79)

How was tone of the article (e.g. positive, indifferent) determined?

REPLY: We have extended the methods with the following details about how the newspaper sentiment was determined:

‘Positive sentiment was noted when a positive opinion was expressed, or when the article described actual implementation of vaccination of school teachers. A negative opinion or non-implementation were considered as a negative sentiment. When articles did not have a clear overall sentiment because a combination of positive and negative opinions was expressed in the article, we considered the sentiment “multiple”.’ (supplement S4, page 1, lines 32-36)

Line 387 - "we adjusted this number" - How was this adjustment done? What assumptions were made?

REPLY: This information was indeed missing. We have now added the explanation to the methods section as follows:

‘Because influenza sick leave and influenza-like illness can be caused by respiratory pathogens other than influenza, we further adjusted these rates by multiplying them by the proportion of specimens testing positive for influenza from sampled patients with influenza-like illness who visited a GP [32-34]. This proportion was from the total Dutch population, as teacher-specific data was not available.’ (Page 9, lines 158-162)

Discussion

Much of the first paragraphs in the discussion are repetition of what was presented in the scoping review section of the results.

REPLY: We certainly agree with the reviewer. The scoping review results have now been shortened to a very brief summary with all further details placed in supplements (S1-S4), as was suggested by both reviewers. This removes any repetition that was present in the body text. The main points now only remain discussed and placed into perspective in the discussion section.

Estimates of cases averted and absenteeism have been in the US, but don't seem to be mentioned in the discussion.

REPLY: These estimates are indeed available for the USA, albeit not specifically for teacher populations, and should indeed be mentioned. We have now added a reference to estimates in USA health care workers by referring to a review paper that reviewed multiple papers on this topic:

‘Also, a review study of health care workers concluded that the incidence of absenteeism due to influenza-like illness was reduced and its duration shortened in those vaccinated, but an estimate of the magnitude of reduction was unavailable [58].’ (Page 22, lines 422-425)

Overall

In my opinion, the scientific value of this paper is really in the impact assessment. I would reframe the narrative throughout to focus on that, minimizing the scoping review. This would mean a very brief summary of the scoping review methods and results, with most of the detail moved to the supplementary materials. In contrast I think much more detail is needed in the methods section for the impact assessment. Similarly the results section should focus primarily on the impact assessment instead of burying that material at the end after a detailed descriptions of the review.

REPLY: We agree with reviewer 2, whose comments are in line with reviewer 1. We adjusted the manuscript to focus mostly on the impact assessment and we moved much of the scoping review methods and results to the supplements (see supplements S1-S4). As the reviewer suggests, only a brief summary of the scoping review methods and results now remains in the main manuscript. In the manuscript we now elaborated much more on the methods and results of the impact estimation (page 9-10, lines 144-174 and page 11-19, lines 208-348). We also included an additional figure explaining the impact calculations (figure 2).

Reviewer #2: Review

In this study, the authors conducted a comprehensive review on flu vaccination administered to school teachers and evaluated its requirements and rationale. I consider that this study’s objectives were (at least partially) achieved by using a combination approach of scoping review, interview, and impact estimation. However, this study is very complex because many issues and study methods are handled in the same paper. I believe this paper is worth publishing. However, some attempts to improve the readability are needed.

REPLY: We thank the reviewer for their opinion that the paper is worth publishing if readability is improved. We made large adjustments to improve the readability. The scoping review (including the interviews) is now only briefly summarized in the body text (with reference to supplements S1-S4 for details), which greatly reduces the complexity of the manuscript. Additionally we elaborated the methods and results sections of the impact estimation to better clarify that topic (page 9-10, lines 144-174 and page 11-19, lines 208-348).

1. In my opinion, scoping review, interview (qualitative study), newspaper search, and impact estimation (modeling) seem different. Since the study consisted of synthesizing these four different studies, this manuscript looks like a policy document rather than an academic write-up. To clarify the scope of each study part, I suggest that the authors explain the aims and reasons for which this method was selected in every part.

2. In addition, the deductive theory flow in this study is as follows: 1. There is a lack of school teachers in Netherlands –> 2. The flu outbreaks worsen this situation –> 3. vaccine could save this situation –> 4. Currently, vaccination is not satisfactorily performed -> 5. So how can we do it? I consider this flow to be inconsistent in this manuscript in each part, leading to a decrease in readability. Therefore, I believe that being conscious of this flow can help readability.

REPLY: We certainly agree that the flow was not clearly explained in the manuscript. We therefore substituted the final paragraph of the introduction by a concise description of the flow:

‘Although Dutch media have recently reported on influenza vaccination of teachers as one way to decrease schoolteacher shortages, a comprehensive overview of literature is lacking. Therefore, we describe the current knowledge of teacher influenza vaccination using very broad input (scientific literature, grey literature, Dutch newspaper reports and information from key informants). Since knowledge of the impact of this vaccination in teacher populations is crucial for decision-making, but is lacking, we then estimated its potential impact.’ (Page 7, lines 116-121). We did not refer to reviewers points 4 and 5 as they were not part of the opinion or the scope of this manuscript. To better clarify this we added a sentence to the introduction:

‘Traditional risk groups targeted for influenza vaccination in many countries include the elderly (60+) and persons with underlying chronic conditions, because of their higher risk of influenza complications. In the Netherlands, this does not include teachers unless they are individually targeted because of fitting one of those traditional risk groups.’ (Page 6, lines 91-94). Also, touching on that topic, we do make a recommendation in the conclusion: ‘Teacher surveys, in-depth cost-effectiveness studies and a pilot at-school influenza vaccination programme could provide critical information about teacher vaccination.’ (Page 25, lines 485-486).

3. Did the author know the low vaccine prevalence in Amsterdam before this survey was performed? If the authors knew this fact before the survey, I think they should mention the low vaccine prevalence in the Introduction section. This is because the low vaccine prevalence could explain the reason for this study and its rationale naturally.

REPLY: Teachers are not a target group for influenza vaccination in the Netherlands. We agree that this was not very clearly stated and we have added the following to the introduction:

‘Traditional risk groups targeted for influenza vaccination in many countries include the elderly (60+) and persons with underlying chronic conditions, because of their higher risk of influenza complications. In the Netherlands, this does not include teachers unless they are individually targeted because of fitting one of those traditional risk groups.’ (Page 6, lines 91-94).

An important reason for the study was the media attention for the potential of decreasing teacher shortages by influenza vaccination and one public health physician wondering if teacher vaccination would actually have an impact on teacher absenteeism. As little seemed known about influenza vaccination specifically in the teacher group we decided to perform a scoping review to provide an overview of the current knowledge on this topic and to identify knowledge gaps more accurately than from hearsay. The main knowledge gap that came forward was the lack of knowledge on the potential impact of teacher vaccination. Therefore we complemented the study with an impact estimation. We have now summarized this in the final paragraph of the introduction as follows:

‘Although Dutch media have recently reported on influenza vaccination of teachers as one way to decrease schoolteacher shortages, a comprehensive overview of literature is lacking. Therefore, we describe the current knowledge of teacher influenza vaccination using very broad input (scientific literature, grey literature, Dutch newspaper reports and information from key informants). Since knowledge of the impact of this vaccination in teacher populations is crucial for decision-making, but is lacking, we then estimated its potential impact.’ (Page 7, lines 116-121).

4. In the Introduction section, the authors mentioned “overviewing any aspect vaccinating teachers against influenza,” however, the aim of the scoping review is identifying “gaps” between existing evidence and required evidence to state the specific purpose of scoping. Therefore, the authors should first define the aim of this scoping review. In this study, I understand that this scoping review aimed to collect evidence on the spread of flu vaccinations among school teachers.

REPLY: We agree that this final paragraph of the introduction was not clear. In the beginning of the introduction we added the information that in the Netherlands, teachers are not targeted for influenza vaccination. And we have replaced the unclear final paragraph by the following: ‘Although Dutch media have recently reported on influenza vaccination of teachers as one way to decrease schoolteacher shortages, a comprehensive overview of literature is lacking. Therefore, we describe the current knowledge of teacher influenza vaccination using very broad input (scientific literature, grey literature, Dutch newspaper reports and information from key informants). Since knowledge of the impact of this vaccination in teacher populations is crucial for decision-making, but is lacking, we then estimated its potential impact.’ (Page 7, lines 116-121).

5. Regarding this scoping review, did the authors identify regions with inadequate vaccination evidence based on the author’s purpose? This seems to be mentioned in the Conclusion section, although I could not find it in the main text.

REPLY: Influenza vaccination for school teachers in not nationally recommended in the Netherlands. We agree that this is not entirely clear from the conclusion section. To clarify this, we have added a sentence in the introduction and we have now emphasized this in the conclusion section as follows (see bold/italic typing):

In the introduction:

‘Traditional risk groups targeted for influenza vaccination in many countries include the elderly (60+) and persons with underlying chronic conditions, because of their higher risk of influenza complications. In the Netherlands, this does not include teachers unless they are individually targeted because of fitting one of those traditional risk groups.’ (Page 6, lines 91-94).

In the conclusion:

However, most of the research was conducted in the USA, where influenza vaccination is already officially recommended for all citizens (excluding infants <6 months) and vaccination uptake is generally higher than in Europe. Grey literature showed that a few European countries nationally recommend influenza vaccination for teachers. In the Netherlands, no municipality, except Amsterdam in 2018 and 2019, was found to offer free influenza vaccination to teachers. However, multiple Dutch school boards do offer vaccination to their personnel, according to key informants and some newspaper articles. The main motivation for the offer was a reduction in absenteeism, but vaccine uptake levels were unreported. Unfortunately, details on how and where vaccinations were provided were either not known or not given. (page 20, lines 357-365)

6. The review of newspapers did not have an impact on the integrity of this study. Additionally, I do not know the scientific validity of these methods. Therefore, it may be better to remove this part from this study.

REPLY: The grey literature did not provide a full overview of the Dutch media attention for teacher influenza vaccination. Therefore we added a search of a Dutch newspaper database. We have removed almost all details on this topic from the manuscript to supplementary S4. This does indeed not impact the integrity of the main manuscript. As the media attention for influenza vaccination as a way to reduce teacher shortages was one of the reasons for this study we feel it best to still provide these details, but in a supplementary.

7. In the impact estimation part, statements that should be written in the Methods section are frequently seen in the Results section (model selection, way of adjustment, etc.). Please consider ameliorating this structure.

REPLY: We agree with the reviewer and we therefore moved those sentences to the methods section.

8. The conclusion is unclear. It could be understandable if the objectives of each part of this study are made intelligible.

REPLY: We agree that this needed more clarity. To this end several sections were modified: the final paragraph of the introduction (to clarify the objectives), the first paragraph of the methods was shortened and simplified (also to clarify the objectives), and a few small clarifications were added to the final paragraph of the discussion:

In introduction:

‘Although Dutch media have recently reported on influenza vaccination of teachers as one way to decrease schoolteacher shortages, a comprehensive overview of literature is lacking. Therefore, we describe the current knowledge of teacher influenza vaccination using very broad input (scientific literature, grey literature, Dutch newspaper reports and information from key informants). Since knowledge of the impact of this vaccination in teacher populations is crucial for decision-making, but is lacking, we then estimated its potential impact.’ (Page 7, lines 116-121).

In methods:

‘We conducted a scoping review of the considerations for and impact of influenza vaccination of school teachers. We then estimated the potential impact of teacher vaccination in the Netherlands at different scenarios of vaccine uptake for three influenza seasons (2016-2019).’ (Page 8, lines 123-125)’

In Discussion:

‘In conclusion, international scientific literature on influenza vaccination of teachers remains sparse and vaccination of this group is not nationally advised in most countries. However, Dutch media attention is growing, sparked by teacher shortages in recent years. The impact of vaccinating teachers has been particularly understudied, although some key experts and media reports have stated that any school board or other entity that is considering offering influenza vaccination to teachers needs to understand the impact of the vaccination. Our estimates showed that vaccinating teachers against influenza might be associated with a substantial decrease of sick leave days due to that viral infection. Teacher surveys, in-depth cost-effectiveness studies and a pilot at-school influenza vaccination programme could provide critical information about teacher vaccination.’ (page 25, lines 478-486)

________________________________________

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Yoshiki Kusama

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

________________________________________

In compliance with data protection regulations, you may request that we remove your personal registration details at any time. (Remove my information/details). Please contact the publication office if you have any questions.

Submitted filename: Response to reviewers.docx

Click here for additional data file.

30 May 2022

10 Jul 2022

Dear PLOS ONE,

Thank you for your queries and for sending us the favourable evaluation of both reviewers. We gladly addressed the minor concerns raised by them as described below. We hope that we have adequately addressed their concerns. Feel free to contact us would there be any remaining queries.

________________________________________

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: No

Reviewer #3: Yes

The underlying data is indeed rather spread out across the manuscript. It is all available in multiple tables which can be found in the 5 supplements as follows:

1. Scientific literature: table S1.2

2. Grey literature: table S2.3

3. Interviews: table S3.1

4. Newspaper monitoring: table S4.2

5. Impact estimate: input parameters available in table 1 in the main manuscript and table S5.1, S5.2, and S5.3 in supplements 5.

________________________________________

6. Review Comments to the Author

Reviewer #2: The authors have corrected their manuscript appropriately in accordance with my suggestions. The readability of the manuscript was dramatically improved by these revisions. However, the Discussion section is excessively long compared to the contents of the study. The following sentences are possibly omitted (or written more briefly). Please consider if the sentences should be removed or left.

Page 20, Lines 362–366

The other research…for teachers.

Page 21, Lines 380–384

Some key information…it are unknown.

Page 21, Lines 389–391

Future research…influenza vaccination.

Page 22, Lines 405–412

In 2019,…in the education sector.

Pages 22–23, Lines 421–423

These are relevant…on working days lost.”

Page 23, Lines 432–437

In school children…in older age.

I suggest that following sentences should be moved.

Pages 24–25, Lines 470–475

Our interview…other than nationally.

Page 22, Line 413 (because the sentences are not relevant to the impact estimation)

Thank you. We now shortened the discussion by removing and shortening sentences. And we made some sections clearer by cutting sentences into two. In detail, the following changes were made:

- “The other research articles mainly assessed teachers’ attitudes towards influenza vaccination and the vaccination uptake in this group. However, most of the research was conducted in the USA, where influenza vaccination is already officially recommended for all citizens (excluding infants <6 months) and vaccination uptake is generally higher than in Europe. Grey literature showed that a few European countries nationally recommend influenza vaccination for teachers.” WAS CHANGED TO: “The other 11 papers mainly assessed teachers attitudes and uptake, mostly in the USA Grey literature showed that a few European countries nationally recommend influenza vaccination for teachers.”

- “Some key informants viewed financial incentives as unnecessary or undesirable, but these incentives were reported in grey literature to increase vaccination uptake. Rotterdam decided not to offer free vaccination to teachers after consultation with school boards . Although vaccination uptake and its predictors have been studied in health care workers [50, 51], Dutch teachers’ knowledge of influenza vaccination and their attitudes regarding it are unknown.” WAS CHANGED TO: “Some key informants viewed financial incentives as unnecessary or undesirable, but these incentives were reported in grey literature to increase vaccination uptake. While vaccination uptake and its predictors have been studied in health care workers [50, 51], Dutch teachers’ knowledge of influenza vaccination and their attitudes regarding it are unknown.”

- “Future research should focus on estimating the effect of vaccinating teachers on sick leave, as many key informants expressed the need for understanding the potential impact of teacher influenza vaccination.” WAS CHANGED TO: “Many key informants expressed that they needed to know the potential impact of teacher influenza vaccination. Future research should also focus on estimating the effect on sick leave of vaccinating teachers.”

- “In 2019, teacher shortages were 3.4%, 2.7% and 2.0% in the large cities of Amsterdam, Rotterdam and The Hague, respectively; in 2020 increases were expected in those cities to 8.4%, 6.6% and 4.7%, respectively [11]. In these three cities, requests have come from either the council’s education department (Amsterdam) or a political party (Rotterdam and The Hague) to set up a vaccination programme for school teachers or to investigate the feasibility of such a plan. While Dutch health care workers [51, 52] are offered free influenza vaccination to protect their vulnerable patients, decreased absenteeism and uninterrupted care are considered additional benefits [53]; this outcome could be similar in the education sector.” WAS CHANGED TO: “In 2019, teacher shortages were 3.4%, 2.7% and 2.0% in the large cities of Amsterdam, Rotterdam and The Hague, respectively. In 2020 these numbers were expected to reach 8.4%, 6.6% and 4.7%, respectively [11]. In these three cities, requests have come from either the council’s education department (Amsterdam) or a political party (Rotterdam and The Hague) to set up a vaccination programme for school teachers or to investigate the feasibility of such a plan. While Dutch health care workers [51, 52] are offered free influenza vaccination to protect their vulnerable patients, decreased absenteeism and uninterrupted care are considered additional benefits [53]. This outcome could be similar in the education sector for which potential uptake and predictors are not yet known.”

- “These are relevant results, as confirmed in a more recent Cochrane review from Demicheli (2018): “ We are uncertain about the effect of inactivated vaccines on working days lost.” WAS CHANGED TO: “These are relevant results, as there is uncertainty about the effect of vaccines on working days lost.”

- “In school children, influenza vaccination showed a positive effect on overall influenza morbidity, not only in schools [59] but also in the community [43, 60]. For the 2009 H1N1 influenza pandemic, it was found that vaccinating school children decreased absenteeism of both teachers and students [61]. Although we focused our research on short-term effects of influenza vaccination, it is important to note that a discussion is ongoing about the long-term effects of repeated vaccination at a young age, which might increase risk of influenza in older age [62].” WAS CHANGED TO: “In school children, influenza vaccination showed a positive effect on overall influenza morbidity, not only in schools [59] but also in the community [43, 60]. For the 2009 H1N1 influenza pandemic, it was found that vaccinating school children decreased absenteeism of both teachers and students [61].”

- “Our interviews found that Rotterdam school boards considered free influenza vaccination for their teachers, and some even implemented it. These school boards did not appear in our newspaper search (see S4), and therefore, it is to be expected that more school boards in the country offer their personnel influenza vaccination. Two foreign news articles (Australia and UK) also illustrate that, although teacher influenza vaccination is neither nationally advised nor offered for free, it is sometimes organized other than nationally [66-69] (see S1).” This was completely moved to supplement 3.

- The two sentences starting at line 413 are about how our impact estimation compares to the (little) available other research. Therefore we would prefer to leave it in the manuscript: ‘Although very limited data are available on the impact of influenza vaccination of specifically school teachers and staff on absenteeism, research has been reported on healthy adults in the general population. A Cochrane review by Demicheli 2014 found that in healthy adults, at least 71 people required vaccination to prevent one laboratory-confirmed case of influenza (CI: 64 to 80)[54].’

Reviewer #3: The authors have come up with an interesting way of bringing forth the impact of vaccination on teachers’ attendance in the Netherland. They have provided supporting data from various sources. This makes it worth publishing.

The authors have answered all the questions put forth by the earlier reviewers and made the necessary changes to the manuscript. They have edited the paper to see that the language used is grammatically correct. Also, they have changed the overall design by concentrating on the impact of influenza vaccination on the Netherlands’ teachers. The tables are very informative in understanding the calculations. The Result section provides all details. The supplementary data is in detail with relevant tables. The authors have put a lot of effort into this project and the information available is ample. They have correctly added the information associated with scoping review in the supplementary section.

The authors have put a lot of effort into correcting the language as well as reducing the content. Yet, the current version needs some more language polishing. Especially for better understanding. The most common issue I found was the sentences are too long. Breaking up the sentences will be helpful.

Below are a few examples of long sentences as well as grammatically incorrect one that needs to be rephrased into smaller sentences.

Line 110: some individual companies and organizations encourage their educational staff

111 to be vaccinated. For example, Amsterdam has offered free vaccination to schoolteachers since

112 2018/2019.

Line 112 rephrase

Line 114 “A review protocol was not registered for this study.”: rephrase

Line 203 “hits in dutch newspaper” rephrase

Line 257 “Absenteeism duration is measured yearly in nearly the total Dutch teacher population” : rephrase

Line 391-396: Long sentences

Line 405-407 Break up into two sentences

Line 419 However, at the perhaps earlier disease stage of sick leave for influenza, our results indicate that only 3.5-9.1 vaccinated teachers were needed to prevent 1 day of teacher influenza sick leave. Rewrite the sentence

Line 423 – 426 Too long

Line 428-431 Too long

Line 454 rephrase

Line 475 rephrase

Thank you. The full manuscript was revised by two of the authors. Long sentences were rewritten to make them more readable. Others were shortened. Most changes follow the reviewers above suggestions which were changed as follows:

- “In the absence of national guidance on influenza vaccination in the educational system, some individual companies and organisations encourage their staff to be vaccinated. For example, Amsterdam has offered free vaccination to schoolteachers since 2018/2019.” WAS CHANGED TO: “In the absence of national guidance on influenza vaccination in the educational system, some local companies and organisations encourage their staff to be vaccinated. For example, in Amsterdam, the public health service has offered free vaccination to schoolteachers since 2018/2019.”

- “A review protocol was not registered for this study.” This sentence is indeed redundant and out of context. As this information is available in supplement 6 we removed this sentence.

- “hits in Dutch newspapers” WAS CHANGED TO “the number of reports in Dutch newspapers”.

- “Absenteeism duration is measured yearly in nearly the total Dutch teacher population” WAS CHANGED TO: “Absenteeism duration is measured yearly in almost all Dutch teachers”.

- “For this, our impact calculations provide an initial estimate of sick leave due to cases of influenza infection that might be averted by vaccinating teacher population; the reduction in sick leave could be considerable with a moderate to high vaccination uptake. Future research should additionally focus on the cost-effectiveness of teacher vaccination both for schools and for public health generally, and it would ideally consider the potential effects of easier accessibility and financial incentives on the uptake.” WAS CHANGED TO: “Our impact calculations provide an initial estimate of influenza sick leave that might be averted by vaccinating the teacher population. The reduction in sick leave could be considerable with a moderate to high vaccination uptake. Future research should additionally focus on the cost-effectiveness of teacher vaccination both for schools and for public health generally. Ideally it would also consider the potential effects of easier accessibility and financial incentives on the uptake.”

- “In 2019, teacher shortages were 3.4%, 2.7% and 2.0% in the large cities of Amsterdam, Rotterdam and The Hague, respectively; in 2020 increases were expected in those cities to 8.4%, 6.6% and 4.7%, respectively [11]” WAS CHANGED TO: “In 2019, teacher shortages were 3.4%, 2.7% and 2.0% in the large cities of Amsterdam, Rotterdam and The Hague, respectively. In 2020 these numbers were expected to reach 8.4%, 6.6% and 4.7%, respectively [11]”

- “However, at the perhaps earlier disease stage of sick leave for influenza, our results indicate that only 3.5-9.1 vaccinated teachers were needed to prevent 1 day of teacher influenza sick leave.” WAS CHANGED TO: “Laboratory testing and physician consultation might occur relatively late in the disease process. At the earlier disease stage of taking sick leave for influenza, our results indicate that only 3.5-9.1 vaccinated teachers were needed to prevent 1 day of teacher influenza sick leave.”

- “Our relatively high estimates of potentially averted absenteeism in teachers may be likely, given the conclusion of Nichol et al (1995) that immunization decreased absenteeism from work due to upper respiratory illness by 43% and absenteeism due to all illnesses by 36% in healthy, working adults [56].” WAS CHANGED TO: “Our relatively high estimates of potentially averted absenteeism in teachers may be likely, given the conclusion of Nichol et al (1995). They reported that immunization decreased absenteeism from work due to upper respiratory illness by 43% and absenteeism due to all illnesses by 36% in healthy, working adults [56].”

- “Also, a review study of health care workers concluded absenteeism due to influenza-like-illness was reduced and its duration shortened in those vaccinated, but an estimate of the magnitude of reduction was unavailable [58].” WAS CHANGED TO: “Another review study of health care workers concluded that absenteeism was less frequent and shorter in those vaccinated, but the magnitude of this reduction was unavailable [58].

- “As some teachers were eligible for influenza vaccination because of age (60+) or underlying medical conditions, we expect that we have underestimated, rather than overestimated, impact of vaccinating teachers.” WAS CHANGED TO: “But, some teachers probably had received vaccination from their GP because of age (60+) or underlying medical conditions (within the general immunization programme). The actually registered sick leave that we used as input parameter would have been higher had they not been vaccinated within the general immunization programme. Therefore, we expect that we have underestimated, rather than overestimated, impact of vaccinating teachers.

- “Two foreign news articles (Australia and UK) also illustrate that, although teacher influenza vaccination is neither nationally advised nor offered for free, it is sometimes organized other than nationally [66-69].” WAS CHANGED TO: “Two foreign news articles (Australia and UK) also illustrate that, although teacher influenza vaccination is neither advised nor offered for free at a national scale, it is sometimes organized locally [66-69]”. This paragraph was moved to supplement 3.

________________________________________

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Yoshiki Kusama

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

________________________________________

In compliance with data protection regulations, you may request that we remove your personal registration details at any time. (Remove my information/details). Please contact the publication office if you have any questions.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

19 Jul 2022

Influenza vaccination of school teachers: a scoping review and an impact estimation

PONE-D-20-40234R2

Dear Dr. Huiberts,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Shinya Tsuzuki, MD, MSc

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All comments raised by reviewers were now appropriately answered.

Reviewers' comments:

2 Aug 2022

PONE-D-20-40234R2

Influenza vaccination of school teachers: a scoping review and an impact estimation

Dear Dr. Huiberts:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Shinya Tsuzuki

Academic Editor

PLOS ONE