Post Introduction Evaluation of the Malaria Vaccine Implementation Programme in Ghana, 2021

doi:10.21203/rs.3.rs-2343963/v1

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Post Introduction Evaluation of the Malaria Vaccine Implementation Programme in Ghana, 2021

https://doi.org/10.21203/rs.3.rs-2343963/v1

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published 29 Mar, 2023

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Background

Malaria remains a public health challenge in Sub-Saharan Africa with the region contributing to more than 90% of global cases in 2020. In Ghana, the malaria vaccine was piloted to assess the feasibility, safety, and its impact in the context of routine use alongside the existing recommended malaria control measures. To obtain context-specific evidence that could inform future strategies of introducing new vaccines, a standardized post-introduction evaluation (PIE) of the successes and challenges of the malaria vaccine implementation programme (MVIP) was conducted.

Methods

From September to December 2021, the WHO Post-Introduction Evaluation (PIE) tool was used to conduct a mix method evaluation of the pilot introduction of the malaria vaccine in Ghana. To ensure representativeness, study sites and participants from the national level, 18 vaccinating districts, and 54 facilities from the seven pilot regions were purposively selected. Data was collected using a questionnaire based on the PIE tool. We performed summary descriptive statistics on quantitative data, thematic analysis on qualitative data, and triangulation of the results from both sets of analyses.

Results

About 90.7% (49/54) of health workers stated that the vaccine introduction process was smooth and contributed to an overall improvement of routine immunization services. About 87.5% (47/54) of healthcare workers, and 95.8% (90/94) of caregivers accepted RTS,S malaria vaccine. Less than half [46.3%; (25/54)] of the healthcare workers received training prior to the introduction but almost all [94.4%; (51/54)] were able to constitute and administer the vaccine appropriately. About 92.5% (87/94) of caregivers were aware of the RTS,S introduction but only 44.0% (44/94) knew the number of doses needed for maximum protection. The initial phase was characterized by low vaccine uptake due to caregiver hesitancy, but coverage improved steadily over the pilot period.

Conclusions

The malaria vaccine has been piloted successfully in Ghana. Intensive advocacy; community engagement, and social mobilization; and regular onsite supportive supervision are critical enablers for successful introduction of new vaccines. Stakeholders are convinced of the feasibility of a nationwide scale up using a phased subnational approach taking into consideration malaria epidemiology and global availability of vaccines.

Malaria

RTS

S vaccine

Pilot

Post Introduction Evaluation

Malaria Vaccine Implementation Programme

Mosquirix

Malaria is a life-threatening disease caused by five species of mosquito-transmitted parasites in humans [1]. In 2020, an estimated 241 million cases of malaria were recorded globally with 627,000 deaths. Children under five years are the most vulnerable and accounted for 80% of the mortalities, of which Africa accounted for 95% of cases and 96% of deaths [2].

In Ghana, malaria accounts for approximately 30% of outpatient attendance and 23% inpatient admissions [3]. Plasmodium falciparum is the predominant malaria parasite in Ghana, accounting for approximately 80–90% of severe morbidity and mortality. Generally, there is a stable transmission pattern. Studies conducted in 2014 and 2019 have shown endemicity ranging from intermittent transmission in the Greater Accra Region to intense seasonal transmission in the Upper West Region and seasonal transmission in the rest of the country [4, 5]. Ghana has made significant strides in malaria prevention and control with existing interventions, contributing substantially to a reduction in malaria-related mortalities. However, the disease burden remains significant, and deployment of additional tools may facilitate achievement of elimination status.

A well tolerated and effective vaccine with an acceptable safety profile could be a potentially important intervention for malaria control. The RTS,S/AS01 malaria vaccine, also known as Mosquirix™, is currently the only malaria vaccine to have received pre-qualification by the World Health Organization (WHO) [6]. The clinical development of the vaccine spanned over 30 years. The pilot implementation programme was recommended by the WHO in 2016 after review of results from the pivotal Phase III clinical trials and the positive scientific opinion by the European Medicines Agency (EMA) under article 58. The pilots were designed to evaluate the public health benefit of the vaccine by assessing the feasibility of delivery, safety and impact on disease morbidity and mortality in the context of routine use alongside other currently recommended malaria control measures.

Based on the positive results from the pilots in Ghana, Kenya, and Malawi, in October 2021, the WHO advisory bodies for immunization and malaria recommended the use of the RTS,S/AS01 malaria vaccine for the prevention of P. falciparum malaria in children living in areas of moderate to high transmission as defined by the WHO. There is also strong evidence of high efficacy of the vaccine using seasonally timed vaccinations in areas where malaria transmission is highly seasonal [7].

Although the Ghana Health Service (GHS) and partners conducted routine monitoring and supportive supervision as part of the introduction process, a standardized post-introduction evaluation (PIE) expected to be carried out six to 12 months after the vaccine introduction was delayed due to competing activities in the wake of the COVID-19 pandemic. The main objective of this evaluation was to assess success and challenges of the malaria vaccine implementation programme (MVIP) and to provide recommendations for introduction of new vaccines in the future.

Malaria vaccine implementing areas

Ghana had 10 regions until 2019 when six new ones were carved out of four of the old regions. Presently, the country has16 regions and 261 districts. The total population according to the 2021 population and housing census was 30.8 million with children under five years constituting approximately 20%.

The vaccine was introduced in 42 out of 76 districts in Brong Ahafo (now divided as Bono, Bono East, and Ahafo), Central, Volta (presently split as Volta and Oti), and Upper East regions (Fig. 1). In six of the 42 districts, GSK-led a Phase IV observational study. The remaining 51 districts in the pilot regions served as comparator sites. The selection of the regions was based on high malaria burden (≥ 20%); high immunization coverage; and high number of age-eligible children to receive the vaccine.

Study design

The WHO Post-Introduction Evaluation (PIE) tool [8] was adapted and a mixed study was carried out from September to December 2021. The PIE tool provides a systematic method for evaluating the outcome of a vaccine introduction on the existing immunization system in a country. It is designed for immunization managers in countries that have introduced new or underutilized vaccines. It focuses on a range of programmatic aspects, such as pre-introduction planning, vaccine storage and wastage, logistics of administering the vaccine, and community receptiveness to the vaccine.

Sampling of study sites and participants

Study sites were purposively selected using pre-defined criteria (vaccination coverage, geographical settings, and regional representativeness). The selection criteria included setting (rural, peri-urban, and urban); immunization coverage (high and low uptake of 2020 RTS,S 1 using a coverage of 70% as cut off); and geographical spread (study sites were equitably selected from all implementing regions). The national level, three regions, 18 districts and 54 facilities, and 90 caregivers were selected for the evaluation (Fig. 2).

Data collection

Desk review was conducted to provide context to the malaria vaccine and its introduction in Ghana. Administration of questionnaires and checklists; observation of practices; and record reviews were carried out at all levels of the health service, including cold and dry vaccine storage areas and points of vaccination, such as health facilities. At the national, regional and district levels, the heads of Expanded Programme on Immunization (EPI) were interviewed. At the health-facility level, a combination of EPI supervisors/senior nurses, immunization staff, and caregivers were interviewed. Open Data Kit (ODK) was used to collect data for the survey.

Data analysis

Quantitative data were extracted onto Microsoft Excel 14.0 spreadsheet and exported into Epi Info statistical software (Epi Info version 7.2.2.16, www.cdc.gov>epiinfo) for analysis. Summary descriptive statistics on quantitative data, and thematic analysis on qualitative data were performed. Results were then triangulated from both sets of analyses. Where there were conflicts of thematic classification of data, it was resolved through team discussion and consultation with other field experts.

Ethical Clearance

This study was part of routine activities carried out following introduction of new vaccines in a population and therefore did not require formal ethical clearance. However, administrative permission was obtained from the Ghana Health Service and participating facilities, and informed oral consent sought from respondents. Confidentiality and anonymity were ensured throughout the study by using password protected android devices and computers and keeping hard copy results under lock and key.

1. Pre-implementation planning coverage, drop-out, recording and reporting

In all the pilot regions and districts, there were updated immunization registers and data collection tools that incorporated columns for RTS,S. Eighty-three percent [83%; (45/54)] of the facilities reported RTS,S vaccination data monthly to the next level and 77.8% (42/54) of the staff interviewed knew the accurate formula for calculating coverage. Generally, the coverage of RTS,S decreased sequentially from the first dose to the fourth in all the districts (Fig. 3). Only 22% (4/18) of districts had RTS,S 1 and RTS,S 3 dropout rate below 10%.

2. Training and knowledge of healthcare workers

Less than half [46.3%; (25/54)] of the vaccinating staff received training prior to the introduction but almost all [94.4%; (51/54)] were able to constitute and administer the vaccine appropriately.

3. Supportive supervision

Although 87% (47/54) of facilities benefited from technical supportive supervisory visits in the preceding six months, only 14.9% (8/54) had written feedback. Majority [88.8%; (16/18)] of district level staff had accurate knowledge of the formula for wastage calculation and same proportion of districts had wastage rate below 25%.

4. Advocacy and vaccine acceptance

Majority [92.5%;(87/94)] of caregivers were aware of the RTS,S introduction but only 44% (41/94) had accurate knowledge on the number of doses needed for maximum protection. More than 80% [87.5%; (47/54)] and 95.8% (90/94) of healthcare workers and caregivers respectively accepted RTS,S. The main reasons for delayed vaccination were ‘busy caregiver’ (Fig. 4) and long waiting time at service delivery points (Fig. 5).

5. Vaccine safety monitoring

More than half [55.6%; (30/54)] of the facilities had forms for reporting adverse events following immunization (AEFI) and adverse event of special interest (AESI) but only 22.2% (12/54) had detected at least one AEFI since introduction of RTS,S. About nine out of 10 [91.8%; (86/94)] caregivers were able to mention at least one possible reaction/side effect of the vaccine. There was an observed increase in adverse event reporting following RTS,S introduction.

6. Cold chain, injection safety, and waste management

About 39.0% (7/18) of the districts made changes to the cold chain and vaccine storage system prior introduction of RTS,S and 83% (45/54) of facilities had functional refrigerators. Less than one-third [27.8%; (5/18)] of districts made adjustment in the waste disposal system and 77.8% (42/54) of the facilities had access to incinerator. About 24% (13/54) reported RTS,S stockout in the preceding six months and 3.8% (4/54) had unusable vaccines because they were either expired or at vaccine vial monitor (VVM) stage 3 or 4. Of the 18 districts, 16 had adequate capacity for clean storage of vaccines and vaccine administration equipment.

7. Effect of vaccine introduction on service delivery

Ninety percent of the facilities had ever cancelled critical routine activities due to lack of funds. To this a staff said: “Sometimes we are unable to get money to purchase fuel and had to abandon outreach services. This results in default especially among children living in the hard-to-reach communities”

Majority [90.7%; (49/54)] of health workers affirmed that the process was smooth, and this was supported by the response of an interviewee who said: “My facility did not encounter any challenges and caregivers readily accepted the vaccine. We did not make any special arrangements to integrate the vaccine into routine schedule”.

Health workers believed that the vaccine introduction has improved immunization service. A Community Health Nurse working in a rural facility had this to say: “We had no vaccine refrigerator but thanks to RTS,S we now have one” “The defaulter tracking book is helping us to account for all children we vaccinate to ensure they don’t drop out” – he added. Another staff also said: “The facility motorbike has been unserviceable for some months now and we were unable to visit some of our communities, but we have received a new one courtesy the MVIP”. On the effect of the vaccine on health of children, a health worker said: “the vaccine has reduced the number of under-five malaria cases the facility records monthly”

The malaria vaccine was introduced into the national childhood immunization programme from May 2019 following a rigorous preparatory phase that started in 2009. A Technical Working Group (TWG) was constituted in 2012 with key function to compile and evaluate evidence on the use of a malaria vaccine in Ghana after the phase III trials were launched. A technical brief was prepared to support informed decision-making for RTS,S based on positive opinions from WHO and European Medicines Agency (EMA) on the results of the phase III trials.

In 2015, WHO issued a position paper calling for large-scale pilot implementation of RTS,S in children five to nine months using the four-dose vaccine schedule to be delivered alongside other malaria control interventions in settings of moderate-to-high parasite transmission zones in sub-Saharan Africa [8]. In January 2016, Ghana (as well as Kenya and Malawi) responded to the World Health Organization (WHO) call for national ministries of health to express interest in collaborating in the RTS,S/AS01 malaria vaccine pilot implementation programme, and was reaffirmed in March 2016. Approval of the country’s request was announced by WHO (alongside with Malawi and Kenya) in April 2017 [8].

Substantial investment was made in improving cold chain and transport; capacity building; and social mobilization before and during the pilot. The account of health workers and data from some facilities indicate that the vaccine has contributed to improved under-five malaria morbidity and strengthened immunization service delivery through bridging cold chain logistics and transport gaps in the implementing districts.

Malaria being an important cause of morbidity and mortality among children under five, public acceptance of a malaria vaccine was highly anticipated, but this was not observed in the initial phase of the vaccine introduction. The caregiver reluctance observed in the initial phase of introduction was also observed in Malawi (MVIP PIE, Malawi, 2021; unpublished). The existing caregiver confidence in the EPI might have introduce some complacency in the timing and intensity of advocacy, community engagement, and social mobilization activities given that one of the key driving factors of successful vaccine roll out is timely stakeholder involvement [9]. Although approval of the country’s request for RTS,S was received in 2017, active engagement of caregivers started just around the time of implementation in 2019. In this long intervening period, the information gap was filled with rumours conveyed through social media and other information platforms [10].

Apart from misinformation and disinformation, other factors contributed to the slow uptake of the vaccine. Poor health worker understanding of the eligibility criteria and dosing schedule resulted in missed opportunities as some eligible children were denied service. Additionally, some caregivers relocated to non-implementing areas on socioeconomic grounds and hence, truncated completion of the vaccination remaining doses. Literacy, knowledge of immunization, attitude of caregivers, and geographic mobility are among key factors with significant impact on vaccine uptake [11, 12, 13]. According to the EPI schedule of Ghana, children complete all routine vaccines (for those who do not default) by 18 months [14] and many caregivers often do not attend child welfare clinics thereafter, although vitamin A is administered every six months and growth monitoring continues till, they turn five years. This affected uptake of the fourth dose which is scheduled at 24 months.

The existence of system for continuous staff training is commendable given that nine out of 10 of the staff constituted and administered the vaccine appropriately despite the high attrition of staff trained prior to the vaccine introduction. Peer-to-peer knowledge transfer, supportive supervision and on-the-job coaching, and availability of job aids were among key interventions instituted to ensure staff have adequate knowledge on the vaccine and its management.

The dropout rate for RTS,S 1 and RTS,S 3 dropout rate has been below 10% although there are regional and district disparities. Some caregivers accepted all vaccines except RTS,S although it was available at the vaccination centre. This position was covertly instigated by some health workers who specifically asked caregivers if they wanted their children to receive RTS,S despite same not inquired for other vaccines. Caregivers trust judgment of health workers and communication uncertainties negatively impact uptake of vaccines [15]. Again, erratic shortage of RTS,S vaccines at the facility level due to distribution challenges in some districts affected availability and resulted in missed opportunities for vaccination [16].

The increased reporting of adverse events was because of the improved vaccine safety surveillance following capacity building of health workers at all levels [17]. Building capacity of health workers and providing them with appropriate incentives (equipment, recording tool, transport, etc) often improves ability to detect priority conditions or disease [18, 19] but not without the possibility of apparent increase in the condition of interest due to misdiagnosis [20]. Majority of the reported AEFI were non-serious and the frequently included fever, headache, cough, abdominal pain, and enteritis. Apart from fever, the others were not noted frequently, and this is consistent with the finding of the phase III trial of the vaccine [21].

In the implementing districts, malaria vaccine was often among low performing antigens. Intensification of public education, rumour management, and advocacy soared up caregiver confidence, and coverage is consistently improving. The schedule for the fourth dose has been reviewed from 24 months to 18 months following recommendations by the National Immunization Technical Advisory Group. There is also planned extension of vaccine introduction to the non-vaccinating district (51 in all) in the implementing regions by end of 2022. These new developments will help to address the challenges of uptake and bring coverage up to par with other routine vaccines.

A limitation of the study is that not all implementing districts were included in the evaluation and the findings might not be reliably generalizable for the country. However, this was mitigated using robust selection criteria that ensured representation of all district-groupings with reference to geographical location, coverage, and service delivery enablers and challenges.

The malaria vaccine has been piloted successfully in Ghana and plans are underway to scale up implementation in other parts of the country. Although the initial phase was characterized by low vaccine uptake due to caregiver hesitancy, coverage has improved steadily following intensive advocacy, community engagement, and social mobilization, and onsite supportive supervision. Adequate cold chain capacity; timely and effective advocacy, community engagements, and social mobilization; alignment with existing routine immunization schedules (convenience of dose schedules); robust defaulter tracing mechanism; effective healthcare worker and community education; and regular supportive supervision are among key factors worth considering prior to a nationwide scale up.

AEFI

Adverse Event Following Immunization

AESI

Adverse Event of Special Interest

EPI

Expanded Programme on Immunization

EMA

European Medicine Agency

GHS

Ghana Health Service

GSK

GlaxoSmithKline

MVIP

Malaria Vaccine Implementation Programme

ODK

Open Data Kit

PIE

Post Introduction Evaluation

WHO

World Health Organization.

Ethics approval and consent to participate

This study forms part of routine activities carried out following introduction of new vaccines in a population and therefore did not require formal ethical clearance. However, administrative permission was obtained from the Ghana Health Service (GHS) and participating facilities, and informed oral consent sought from respondents. Approval for oral informed consent was given by the Ghana Health Service Ethics Review Committee. The experimental protocol was approved by WHO and GHS. All methods were performed in accordance with relevant guidelines and regulations. Confidentiality and anonymity were ensured throughout the study by using password protected android devices and computers and keeping hard copy results under lock and key.

Consent for publication

Not applicable

Availability of data and material

The datasets generated and/or analyzed during the study are not publicly available because it is not possible to fully anonymize the transcript files. The experiences shared by the respondents are intrinsically shaped by their specific roles and responsibilities within the implementation making it possible for linkage of responses to respective identities. However, they will be available from the Ghana Health Service through the corresponding author upon reasonable request.

Competing interest

None

Funding

Funding was provided by WHO and PATH.

Authors’ contributions

MAR, KAA, RO, and POT conceptualized the study. JTB, GB, KOAA, RO, and JFD developed the study protocol and tools with inputs from FCK, and FAB. Data collection was supervised by ETS, FOO, and FOA and analysis was conducted by MAR and ETS. The manuscript was conceptualized by EZ, PKA, and KAA and drafted by MAR, BBK, and MJA. All authors contributed to revising the manuscript and approval of the final version. All authors read and approved the final manuscript.

Acknowledgements

We express profound gratitude to all data collectors and staff working at the GHS/EPI, PATH, and WHO for their diverse roles. The authors would also like to thank all health professional and caregivers who participated in this study.

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No competing interests reported.

Download PDF

Journal Publication

published 29 Mar, 2023

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Editorial decision: Major revision
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Reviews received at journal
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Reviewers agreed at journal
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You are reading this latest preprint version

Post Introduction Evaluation of the Malaria Vaccine Implementation Programme in Ghana, 2021

Status:

Journal Publication

Version 1

Abstract

Figures

Background

Methods

Malaria vaccine implementing areas

Study design

Sampling of study sites and participants

Data collection

Data analysis

Ethical Clearance

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1