Feasibility of conducting intradermal vaccination campaign with inactivated poliovirus vaccine using Tropis intradermal needle free injection system, Karachi, Pakistan.

BACKGROUND: Administration of intradermal fractional dose of inactivated poliovirus vaccine (fIPV) has proven to be safe and immunogenic; however, its intradermal application using needle and syringe is technically difficult and requires trained personnel.
METHODS: We assessed feasibility of conducting an intradermal fIPV campaign in polio high risk neighborhood of Karachi using Tropis needle-free injector. During the one-day fIPV campaign, we measured average "application time" to administer fIPV with Tropis, collected ergonomic information and measured vaccine wastage.
RESULTS: Eleven vaccinator teams, after two-day training, immunized 582 children between 4 months and 5 years of age. Average "application time" ranged from 35-75 seconds; the "application time" decreased with the number of children vaccinated from 68 to 38 seconds between 1st and 30th child. 10/11 (91%) vaccinator teams found no ergonomic issues; 1/11 (9%) assessed that it was not easy to remove air bubbles when filling the device. There was 0% vaccine loss reported. No adverse events following immunizations were reported.
INTERPRETATION: We demonstrated that it is feasible, safe and efficient to use Tropis for the administration of fIPV in a campaign setting.

Background

In the last several years, the Global Polio Eradication Initiative (GPEI) has made remarkable strides towards successfully eradicating polioviruses globally. As of April 18, 2017, only 5 cases of poliomyelitis caused by wild poliovirus (WPV) were reported in 2017 from two endemic countries (Afghanistan and Pakistan) while no cases have been reported from the third endemic country (Nigeria) [1]. In order to declare poliovirus eradicated, not only WPV but also polioviruses emanating from the use of oral poliovirus vaccine (OPV) need to be eradicated. This includes OPV (or Sabin) polioviruses as well as vaccine derived polioviruses. Therefore, the use of OPV has to be replaced with inactivated poliovirus vaccine (IPV). As a first step in the Polio Eradication and Endgame Strategic Plan 2013–2018, Sabin strain of poliovirus type 2 contained in the trivalent OPV (tOPV) was withdrawn globally in April 2016; and tOPV was replaced by bivalent OPV (bOPV) containing Sabin strains 1 and 3. In addition, at least one dose of IPV was supposed to be introduced in all countries for risk mitigation purposes [2], however, an unanticipated reduction in manufacturing capacities resulted in an acute shortage of IPV that affected 43 countries and caused either delayed IPV introduction or stock-outs in countries that had already introduced IPV [3, 4]. This global IPV shortage is predicted to last for several years and therefore GPEI started exploring options of how to stretch the existing IPV supply.

Intradermal administration of 1/5th of full dose IPV (0.1 mL instead of 0.5 mL), referred to as fractional IPV (fIPV) has demonstrated good safety and immunogenicity [5, 6, 7, 8, 9, 10, 11, 12]; and can be considered as an important strategy to combat the shortage of IPV by dose sparing in routine immunization or for outbreak response campaigns [13].

While the use of full dose intramuscular administration of IPV in campaigns was successfully demonstrated in Africa, Pakistan and Afghanistan [14], the intradermal use of fIPV in campaign settings was considered to be technically challenging with traditional BCG needles and syringes (considered as “classical intradermal administration performed by insertion of a 26–27 gauge needle nearly parallel to and solely into the skin to raise a visible bleb”). Despite these challenges, a successful fIPV campaign with BCG needle and syringe was carried out in India and in Pakistan in 2016 [15].

In order to overcome the perceived difficulties with use of BCG needle and syringe in campaign settings, new intradermal administration methods are being explored, including Tropis needle-free injection system manufactured by Pharmajet®, (Colorado, USA) (Tropis). This device has been previously tested in polio studies in Cuba and the Gambia. In these studies Tropis has demonstrated its ability to induce equal immunogenicity and injection quality when compared with other intradermal methods; and no safety concerns were identified [7, 16]. So far, however, Tropis has not been evaluated for program feasibility, and safety in campaign setting. The objective of this study was to evaluate the feasibility and safety of Tropis for administering fIPV in campaign setting among children aged 4–59 months in polio high risk area of Karachi, Pakistan.

Methods

Karachi is the biggest metropolitan city of Pakistan and is divided into 18 administrative towns. The study was conducted in one of the low-income areas, Ibrahim Hyderi in Bin-Qasim town − a peri-urban neighborhood, with estimated population of about 150,000. The department of pediatrics and child health of the Aga Khan University (AKU) operates primary healthcare center (PHC) in this area. AKU has well-established demographic surveillance, which captures pregnancies and new births. The PHC provides Expanded Programme of Immunization (EPI) services in liaison with the local town health officer. Children aged 4 to 59 months, living in Ibrahim Hyderi for at least 3 months, whose parent or legal guardian provided informed consent were eligible to be enrolled in this study.

A group of “vaccinators” without any formal training regarding health or injection administration but with at least secondary school certificates were hired. AKU provided two-day training regarding the study protocol, consent taking procedure, IPV, cold chain maintenance, and how to use Tropis. Eleven teams were formed (each team composed of 2 community mobilisers, 1 vaccinator and 1 assistant).

We conducted a one day campaign on December 29, 2016. As per WHO recommendations, temporary outreach vaccination centers in health houses, religious institutions, schools, or offices of the local organizations and houses of the local leaders were established [14]. Vaccinators and their assistants set up vaccination stations in the temporary outreach centers in different locations in the area, while their respective community mobilizers started house-to-house visits to bring children to the temporary vaccination stations. The assistant in each team obtained informed consent. If consent was provided, one dose of fIPV was administered to the selected children using Tropis. The vaccine used was produced by Bilthoven Biologicals, Netherlands and was presented in one-full-dose vials (0.5 mL). The vaccine was administered in the upper arm of the child. The assistant in each team advised the parents to report to the PHC in case of any adverse effect such as unusual pain on the injection site, swelling, redness, rash, fever, vomiting, seizures or any other illness. In addition, the families were visited by AKU workers one and two weeks after the immunization to assess whether any adverse events following immunization were present.

We defined “application time” as timer period from charging of the Tropis until the disposal of the used syringe into a safety box. The “application time” was recorded by the team assistant after each injection. We counted the number of fIPV doses drawn from each IPV vial. After the end of the campaign, each vaccinator filled in a questionnaire evaluating ergonomic features of Tropis.

Approvals from Ethical Review committee of AKU and WHO Geneva were obtained.

Results

The community mobilizers approached 688 households, 63/688 (9.15%) households refused to consent, 19/688(2.76%) households were locked at the time of visit, 24/688 (3.49%) households had no eligible child and 582/688(84.6%) consented to participate in the study. Among the households who consented to participate, 582 children were vaccinated.

There were differences in the total number of children vaccinated by each team. The team with lowest number of vaccinated children immunized 30 children; the highest immunized 75 (Fig. 1).

Fig. 1

Total number of children vaccinated and average time of each team during campaign.

The average “application time” was 48 seconds. The average “application time” decreased with the number of children vaccinated. When taking into account the first 30 children, the average “application time” was 68 seconds for the first child and 38 seconds for the 30th child (Fig. 2).

Fig. 2

Average application time to vaccinate first 30 children with fIPV using Tropis intradermal device.

The average number of fIPV doses drawn from one IPV vial was 5.3. A total of 110 vials were used to vaccinate 582 children. There was no vaccine loss rather 32/582 (5.5%) more children were vaccinated with recommended dose.

All the vaccinators reported that crying among children was less common, filling the device was easy, device was appropriate size, and giving the injection was easy. One vaccinator reported that air bubbles were not easy to remove (Table 1).

Table 1

Ergonomic features of Pharmajet Tropis needle free injection device.

		ResultsN(%)
Number of vaccinators using device		n= 11
Filling	Filling the syringe is easy	11(100%)
	Ability to fill with correct dosage	11(100%)
	Is the device appropriate size	11(100%)
	Air bubbles easy to see	11(100%)
	Easy to remove air bubbles	10(90.9%)
	Comfort while filling syringe(scale:1 = lowest, 5 = highest)	10(5) 1(4)
Delivery	Giving injection is easy	11(100%)
	Comfort while administering injection(scale:1 = lowest, 5 = highest)	9 (5) 2(4)
	Did device hurt wrist or hand	0 (0%)

No adverse events related to the fIPV administration were observed either immediately after immunization or during the weekly monitoring visits for two weeks after the campaign.

Discussion

This study demonstrated that it is feasible, safe and efficient to use Tropis for the administration of fIPV in a campaign setting. The average “application time” and vaccine wastage was superior when compared to other methods of intradermal administration such as BCG needle and syringe or intradermal needle adaptors [17].

Training on how to use Tropis was straightforward and could be completed in several hours. The skills required to use Tropis are easy to understand and do not need any formal health background or prior training in injection administration. The decreasing “application time” with the number of vaccinated children further demonstrated that the experience with the device translates into better efficacy indicating fast learning curve. Unlike campaigns with orally administered OPV the main hindrance for IPV campaigns is the unavailability of large number of health workforce trained in administration, therefore our finding may have important implications for polio program.

There was 0% vaccine loss reported, possibly due to the fact that the IPV manufacturer slightly overfilled the vials with IPV resulting in >5 fIPV doses drawn from 1 vial; and also because the mechanism of Tropis limits the amount of vaccine drawn into the device-syringe at 0.1 mL.

There were some technical difficulties that occurred with several Tropis devices. There were 2 devices with failure in the ejection button (the mechanism to eject the used disposable syringe after injection administration), and 5 devices with either failure of the charging button (the mechanism to charge the device for administration of vaccine using the pressure) alone or both charging and ejection buttons. After this study, the manufacturer of Tropis addressed the identified issues.

Our study provided evidence that fIPV can be successfully used in a campaign using Tropis. The device is safe, efficient in dose sparing, quick in administration of fIPV, and needs minimal training to use in campaign settings.

Declarations

Author contribution statement

Mohammad Tahir Yousafzai, Ali Faisal Saleem, Ondrej Mach, Attaullah Baig, Roland W. Sutter, Anita K.M. Zaidi: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.

Funding statement

This work was supported by The World Health Organization. Dr. Ali F Saleem received research training support from the National Institute of Health’s 127 Fogarty International Center (1 D43 TW007585-01).

Competing interest statement

The authors declare no conflict of interest.

Additional information

No additional information is available for this paper.