Feasibility, uptake, and performance of COVID-19 rapid antigen diagnostic tests among refugees and migrants: Finding from secondary analysis of data from a pilot project in Jordan

doi:10.21203/rs.3.rs-2867817/v1

1) Background: Antigen Rapid Diagnostic Tests (Ag-RDTs) supplements health system’s capacities for COVID-19 testing. Minimal data are available on their use for refugees and migrants. The study aims to describe the feasibility, uptake, and performance of Ag-RDTs among refugees and migrants in Jordan while describing the encountered facilitators and barriers.

2) Methods: A cross-sectional study using data collected from an Ag-RDTs pilot project comprising 17,000 Ag-RDTs in Jordan.

3) Results: About 17,060 people were eligible, of which 99.5% consented. Exactly 99 (0.6%) people were positive. Higher positivity was observed among those with severe COVID-19 symptoms (4.2%) and a history of COVID-19 contact (4.1%). A non-random sample of 209 people underwent confirmatory rt-PCR tests. Observed sensitivity, specificity, positive and negative predictive values of Ag-RDTs were 72%, 97%, 57% and 98.5%, respectively. Key challenges included facing initial hesitancy to undergo Ag-RDTs due to perceived fear of pain, stigma, and isolation, and in getting confirmatory rt-PCR testing.

4) Conclusion: Good feasibility and uptake of Ag-RDTs were demonstrated among refugees and migrants in Jordan. Despite low positivity, certain characteristics were associated with higher rates. Higher specificity and negative predictive values indicate Ag-RDTs can be incorporated within national COVID-19 testingstrategies for ruling out COVID-19.

COVID-19

Ag-RDTs

Refugees

Jordan

MENA

Pandemic Rapid diagnostic tests

1.1 The COVID-19 Pandemic

The COVID-19 pandemic has affected every country worldwide, including middle east Asia and North Africa (MENA) region, which hosts many refugees and migrants. Refugees and migrants often live in high population density areas with inadequate essential facilities, making them susceptible to a COVID-19 outbreak[1]. For example, Jordan has over 720,000 refugees living in different outreach camps, lacking insufficient health services, including limited access to COVID-19 testing[2]. Despite the attempts from The Global Humanitarian Response Plan for COVID-19 to provide a strategic framework to minimize the COVID-19 damage, especially among refugees and migrants in crises, there are considerable implementation gaps due to resource constraints[3].

1.2 Introducing Antigen Rapid Diagnostic Tests (Ag-RDTs)

The development of COVID-19 Ag-RDTs aimed at mitigating the inequality in accessing COVID-19 testing, especially within outreach settings[4]. Ag-RDTs are easy to perform, can yield results in 15–20 min, and are less costly than molecular reverse transcriptase polymerase chain reaction (rt-PCR) based tests[5]. Rt-PCR tests are relatively more accurate than Ag-RDTs but expensive and require laboratory equipment, qualified human resources, skills, and infrastructure[6]. In addition, Ag-RDTs detect most COVID-19 infections within the first week of symptom onset and in those with high viral load. Thus, can have high diagnostic utility in tackling the spread of COVID-19, especially in the early disease phases[7].

1.2.1 Ag-RDTs’ Implementation Gaps

Ag-RDTs are beneficial when rt-PCR tests are unavailable or when the rt-PCR turnaround time is too long to inform clinical decisions and undertake public health measures such as contact tracing[8]. Ag-RDTs can fill gaps in access to testing and reduce pressure on laboratories performing rt-PCR tests, thereby reducing delays in diagnosis, and optimizing the use of available tools. However, concerns about Ag-RDTs being less accurate than molecular tests have resulted in their slower uptake[9]. Modelling studies showed that for screening, test accuracy is secondary to the frequency of testing and rapid result time to interrupt transmission through isolation and contact tracing[10] and this should allay concerns about the Ag RDTs being less accurate than rt-PCRs. However, there is currently little documented programmatic experience describing the feasibility and uptake of Ag-RDTs, especially in the context of refugees and migrants. Moreover, understanding the facilitators and barriers to the Ag-RDTs uptake among refugees in outreach settings is critical. Previous studies from the MENA region indicated that concerns about the financial burden of the test, fear of stigma from the surrounding community, conspiracy theories and “propaganda”[11, 12]may affect the uptake of COVID-19 tests within their population, including Ag-RDTs[13, 14].However, there is limited evidence on such facilitators and barriers within refugees’ and outreach settings[14].

1.3 Response – Ag-RDTs Implementation Project

To understand how Ag-RDTs can be safely and effectively introduced in humanitarian crises, a pilot project was implemented by the International Organization for Migration (IOM) in 2022 through funding and technical support from the Foundation for Innovative New Diagnostics (FIND)[15]. This pilot project comprising 100,000 Ag-RDTs was implemented in certain geographical areas and health facilities in four countries Jordan (17,000 tests), Lebanon (25,000 tests), Iraq (33,000 tests), and North-West Syria (25,000 tests). IOM supports these countries' health ministries to implement TB, HIV and malaria prevention and control among refugees and migrants through the Global Fund’s Middle East Response (MER) project[16]. The number of tests allocated to each country was determined based on local requirements and operational feasibility. This pilot project was positioned to inform interventions for the optimum use of Ag-RDTs to be made available through the Global Fund’s C19RM platform[17] to support the COVID-19 response in these settings.

1.1 Project Objectives

In this context, a study was undertaken in Jordan with two objectives: a) to describe the feasibility, uptake, and results of the Ag-RDTs among eligible persons from refugees and migrants; b) to describe the facilitators and barriers for the use of the ag-RDTs in these settings from the perspective of Community Health Workers (CHWs) involved in conducting the tests. Answering these objectives would lead to a better understanding of the potential utility of Ag-RDTs and their optimum practical application within Jordan and MENA region, especially among refugees and migrant populations.

2.1 Study Design

A cross-sectional design using secondary data collected as a part of the routine recording and reporting, supervision, and monitoring processes of the pilot project.

2.2 The Ag-RDTs Project Implementation in Jordan

2.2.1 Country Setting

Jordan is a country in Western Asia with of population of over 11.2 million people in 2022[18] The country is administratively divided into 12 Governorates[19]. There are over 720,000 refugees and migrants in the country[2].Towards the end of 2022, Jordan reported a cumulative of 1,746,997 confirmed infections and 14,122 cumulative deaths, translating to a case fatality rate of 0.81% [20] Jordan experienced three major waves of transmission since the start of the pandemic, with the last one ending in March 2022[20]

2.2.2 Project Setting

The Ag-RDTs project was implemented in health facilities where IOM provides TB and HIV services to the refugees and migrants through MER[16], in addition to different camps/mobile clinics in four Governorates (Amman, Irbid, Mafraq and Zarqa'a). Two sites (2 Hospitals in Amman and Zarqa’a Governorates) were excluded from the planned list of 19 implementing sites due to lengthy approval processes. A few more facilities and camps in two other Governorates (Ma’an and Ajloun) were included after obtaining related authorities’ approvals to follow the seasonal refugees' movement in Jordan. Experienced CHWs (N = 33) already working on MER with the target communities were trained to perform the WHO prequalified antigen RDT test [Panbio COVID-19 Ag Rapid Test Device ® (Nasal) manufactured by Abbot Diagnostics with a manufacturer-reported sensitivity and specificity of 98.1% and 99.8% respectively] and follow the algorithm given in Fig. 1 to deal with the positive and negative Ag-RDTs results. This algorithm was per the recommendations made by WHO for the use of Ag RDTs in a setting with a low population prevalence of COVID-19 infection[8, 21]

2.3 Eligibility Criteria

Persons from the target communities who fulfilled any of the following eligibility criteria were offered ag-RDTs: a) patients presenting with COVID-19 symptoms to primary health care centers (PHCs), Hospitals and TB centers if they are within seven days of onset of symptoms; in addition to the following eligibility criteria regardless of the presence of symptoms: b) contacts of COVID-19 infected persons; c) refugees and migrants in dense areas; d) healthcare workers; f) any other individuals who voluntarily sought COVID-19 tests through different testing campaigns. Mild COVID-19 symptoms included: fever, cough, sore throat, and nasal congestion, while severe COVID-19 symptoms included: shortness of breath, difficulty breathing, chest pain, impaired consciousness, loss of speech or movement and cyanosis. These eligibility criteria were determined based on the recommendations of the local health authorities.

All screened persons who met any of the eligibility criteria were approached and enrolled on the Ag-RDT project by collecting their general demographic data, including age, sex and vaccination status, and were offered the Ag-RDTs. The Ag-RDTs was conducted to only those who signed the written consent (Additional File 1) to undergo the test. Collecting the general demographic data from all participants, even those refusing to take the test, was to observe the attrition rate and the most likely group characteristics that accepted/declined to undergo the Ag-RDTs.

2.4 Recording and Reporting Data

A recording and reporting system was designed to capture the demographic and clinical characteristics of the persons undergoing the Ag-RDTs. The data were recorded initially in hard copies (logbooks). Then, they were immediately entered into an online digital platform created in the KOBO Toolkit® to enable real-time monitoring of the project implementation. Choosing two recording measures was to double-check the entries in case of any recording error or delayed entries waiting for the rt-PCR result. In addition, apart from COVID-19 Ag-RDT, persons undergoing Ag-RDT tests at non-TB health facilities were assessed, when possible, for tuberculosis (TB) symptoms. Those with TB symptoms were requested to undergo evaluation for TB disease.

2.4.1 Data Monitoring

To supervise and monitor the project implementation at the field level, regular supervisory visits were made by the project coordinator and one field coordinator, during which they interacted with the healthcare workers and persons undergoing the ag-RDT tests. A checklist was used during the supervisory visit. Detailed field visit reports were prepared and used for undertaking any corrective actions. In addition, the project coordinator reviewed the KOBO application entries weekly for gaps in the project implementation or the data entry and provided feedback to address any observed deficiencies.

3.5 Study Population and Study Period

The study included all eligible screened persons who were offered the Ag-RDTs within hospitals, health facilities, TB facilities, camps, and Informal tented settlements, including the project’s CHWs and other related health staff within the health facilities and hospitals. The pilot project was implemented between October and November 2022. The project data analysis was conducted between December 2022 and February 2023.

3.6 Data Variables

For the first objective, the data variables included serial number, name of the health facility, date of enrolment, age, gender, presence or absence of symptoms, the reasons for antigen RDT testing, vaccination status, consent given/not given, the results of ag-RDT test results and date, whether the person was also selected for TB testing and the test results and finally the dates and results of rt-PCR testing if the person has undergone the tests. For the second objective, data gathered during the supervisory visit reports filed by the project and field coordinators were used to obtain information on facilitators and barriers to implementing the antigen RDT tests or its uptake at the field level.

3.7 Data Analysis and Interpretation

For objective 1, the data on the demographic and clinical characteristics of the persons enrolled, those who consented to undergo the tests, and those with positive and negative test results were summarized using frequencies and percentages. We have made inferences on the feasibility by assessing whether the tests could be implemented in all health facilities/camps, informal tented settlements and geographical areas as envisaged per the algorithm. In addition, inferences about uptake have been assessed by the number and proportion of eligible persons who have given consent to undergo the tests. For objective 2, we have provided a narrative description of the lessons learnt and challenges encountered by the health workers in implementing the pilot project as identified by the project coordinators during their supervisory visits.

4. Ethical Statement:

All subjects gave their written informed consent for inclusion in the project implementation and research publication before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Jordan University of Science and Technology–Institutional Review Board in Jordan (Ref.: 45/152/2022) on 25 October 2022.

The demographic and clinical characteristics of all eligible participants, those who consented, and their positivity rates in both numbers and proportions are detailed and were segregated by: Gender and Age group (Table 1), reasons for testing, severity of symptoms and vaccination status (Table 2) and by testing site (Table 3).

Table 1: Characteristics of persons enrolled, consented for Ag-RDTs testing and their positivity rates, segregated by gender and age groups.

Characteristics	Number of persons enrolled		Consented to undergo Ag-RDT		Positive among those tested
	N	%	N	%	N	%
Total	17060	100.00%	16970	99%	99	0.60%
Gender
Female	7078	41.50%	7041	99.50%	35	0.50%
Male	9975	58.50%	9923	99.50%	64	0.60%
Others (recording error)	7	0.00%	6	85.70%	0	0.00%
Age groups
<5 years	1193	7.00%	1191	99.80%	1	0.10%
5-17 years	3849	22.60%	3834	99.60%	19	0.50%
18-34 years	6653	39.00%	6615	99.40%	49	0.70%
35-49 years	3731	21.90%	3708	99.40%	20	0.50%
50-64 years	1381	8.10%	1370	99.20%	9	0.70%
65 + years	253	1.50%	252	99.60%	1	0.40%

5.1 Overview of Totals and Data Segregated by Gender and Age Groups

Overall, 17,060 persons were screened and found eligible to be offered Ag-RDTs. Of which, 16970 consented to take the test. Almost 99.5% have agreed to undergo the test. The uptake was uniformly high among all population sub-groups except those enrolled at Mafraq primary health care center (82.3%). Of those who underwent the Ag-RDT test, 99 peoples tested positive, with an average test positivity of 0.6%. The eligible persons enrolled included relatively more males (58.5%) than females (41.5%), and about 60% were in the 18–50-year age group.

Table 2: Characteristics of people enrolled, consented for Ag-RDTs testing and their positivty rates, segregated by reasons for enrolment, vaccination status, duration and severity of symptoms.

Characteristics	Number of eligible peoples enrolled		Consented to undergo Ag-RDT		Positive among those tested
	N	%	N	%	N	%
Total	17060	100.00%	16970	99%	99	0.60%
Reasons for enrollment for Ag-RDT*
Covid symptoms	2651	15.50%	2646	99.80%	38	1.40%
H/o Contact with a Covid infected person	275	1.60%	266	96.70%	11	4.10%
Health care worker	125	0.70%	123	98.40%	3	2.40%
Recently travelled	65	0.40%	65	100.00%	2	3.10%
TB clinic	2122	12.40%	2121	100.00%	18	0.80%
Admitted at ICU	5	0.00%	5	100.00%	0	0.00%
Respiratory illness	1503	8.80%	1500	99.80%	5	0.30%
Febrile illness	210	1.20%	209	99.50%	1	0.50%
Migrant	3642	21.30%	3638	99.90%	10	0.30%
Refugee	6190	36.30%	6149	99.30%	1	0.00%
Others^#	1635	9.60%	1625	99.40%	29	1.80%
Vaccination status
0 dose	4913	28.80%	4894	99.60%	21	0.40%
One dose	203	1.20%	202	99.50%	0	0.00%
Two doses	11284	66.10%	11215	99.40%	77	0.70%
more than two doses	660	3.90%	659	99.80%	1	0.20%
Duration of symptoms	N=2651**	%	N= 2646$	%	N= 2646$	%
< 7 days	2526	95.20%	2521	99.80%	38	1.50%
> 7 days	125	4.80%	124	99.20%	0	0.00%
The severity of the symptoms	N=2651**	%	N= 2646$	%	N= 2646$	%
Mild	2581	97.30%	2573	99.60%	35	1.40%
Severe	72	2.70%	72	100.00%	3	4.20%

*More than one reason is possible, and the total adds up to more than 100%.

**N here is for all eligible symptomatic.

$: N here is for consented symptomatic only from the total eligible peoples enrolled.

5.2 Data Segregated by Resaons for Testing, Vaccinan Status, Duration and Severity of Symptoms

About 15% of the enrolled persons had COVID-19 symptoms, 8% had a known chronic respiratory illness that is not currently causing any symptoms, and about 1.6% had a history of contact with a known COVID-19 infected person. Apart from these, the major reasons for enrolment were being a refugee (36.3%) or migrants (21.3%) living in high population dense areas. Of all screened participants enrolling in the project, those who had symptoms of COVID-19 infection were 2691 participants. Of these, 95.2% had symptoms of < 7 days, and most (97.3%) had mild symptoms. A minor percentage of participants with symptoms of more than seven days were also included in the enrollment, as discussed in the lessons learnt/challenges section of the results. About 70% of the persons enrolled have taken two or more vaccination doses. Higher positivity was observed among those with severe COVID-19 symptoms (4.2%), history of contact with a covid infected person (4.1%), with recent travel history (3.1%) followed by health care workers (2.4%) who underwent the test.

Table 3: Characteristics of people enrolled, consented for Ag-RDTs testing and their positivty rates, segregated by testing site.

Characteristics	Number of persons enrolled		Consented to undergo Ag-RDT		Positive among those tested
	N	%	N	%	N	%
Total	17060	100.00%	16970	99%	99	0.60%
Covid Ag-RDT testing site
Amman PHC	117	0.70%	117	100.00%	4	3.40%
Amman TB Clinic	2340	13.70%	2328	99.50%	14	0.60%
Amman Camps/Mobile clinics	3430	20.10%	3424	99.80%	6	0.20%
Amman Laboratory	30	0.20%	30	100.00%	0	0.00%
Irbid PHC	45	0.30%	45	100.00%	0	0.00%
Irbid Hospital	26	0.20%	26	100.00%	0	0.00%
Irbid TB Clinic	1442	8.50%	1437	99.70%	1	0.10%
Irbid Camps/mobile clinics	1727	10.10%	1725	99.90%	1	0.10%
Irbid Laboratory	129	0.80%	129	100.00%	1	0.80%
Mafraq PHC	62	0.40%	51	82.30%	0	0.00%
Mafraq Hospital	38	0.20%	38	100.00%	0	0.00%
Mafraq camps/mobile clinic	1223	7.20%	1222	99.90%	8	0.70%
Mafraq laboratory	32	0.20%	32	100.00%	0	0.00%
Mafraq TB Clinic-1	402	2.40%	399	99.30%	1	0.30%
Mafraq TB Clinic-2	58	0.30%	58	100.00%	3	5.20%
Zarqa'a PHC	99	0.60%	99	100.00%	1	1.00%
Zarqa'a TB Clinic	1634	9.60%	1627	99.60%	0	0.00%
Zarqa'a camps/mobile clinic	494	2.90%	482	97.60%	9	1.90%
Others	3732	21.90%	3701	99.20%	50	1.40%

Footnotes: PHC=primary health centre; TB=Tuberculosis; ICU= intensive care units.

5.3 Data Segregated by Testing Site

Most of the enrolment happened at camps/mobile clinics (40.3%), followed by TB centres (34.4%). Approximately 22% of the tests were done in unplanned geographical sites and Governorates after obtaining governmental authorities’ approvals and were categorized under ‘others’. Higher positivity was observed among those enrolled at Mafraq TB clinic (5.2%), those enrolled at Amman PHC (3.4%).

5.4 Performance of Ag-RDTs

Of those who underwent Ag-RDT tests, a non-random sample of 1374 persons also underwent rt-PCR tests based on the simultaneous availability of rt-PCR testing in some health facilities to the consented participants where the Ag-RDTs were conducted (Table 4).

Table 4: Results of confirmatory rt-PCR tests undergone by persons with Ag-RDT results in an antigen RDT pilot project in Jordan, 2022

Antigen RDT tests	rt-PCR tests
Antigen RDT tests	Total who underwent the test	Positive	Negative	Results unknown
Positive	15	8	6	1 (6.6%)
Negative	1359	3	192	1164 (85.6%)
Total	1374	11	198	1165 (84.8%)

This included 15 of the 99 persons (15.1%) with positive Ag-RDT test results and 1359 (8%) of the 16,871 persons with negative Ag-RDT test results. Of those who underwent the confirmatory rt-PCR test (n=1374), the project team could not collect/receive information about the rt-PCR test results of 1165 (85%) persons, predominantly those with negative Ag-RDT results. This was due to the long turnaround of rt-PCR results which could take days in governmental health facilities, making the process of following up the rt-PCR results with all these participants inapplicable. Excluding these people, a total of 209 persons had both antigen-RDT and rt-PCR test results. From this data of 209 persons, the observed sensitivity of the Ag-RDT test was 72% (8/11), specificity was 97% (192/198), positive predictive value was 57% (8/14) and negative predictive value of 98.5% (192/195).

5.5 TB Bi-directional Screening

Eligible persons with COVID-19 symptoms who underwent the test were simultaneously assessed for TB symptoms, and 16 persons were referred for TB tests, of which two new TB cases were identified.

5.6 Leasons learnt/Challenges

The lessons learnt/challenges encountered by health care are listed in Table 5. The key challenges faced were in the domains of identifying eligible populations, especially excluding those with COVID-19 symptoms more than seven days from undergoing the Ag-RDT test, referral for confirmatory rt-PCR testing and obtaining the rt-PCR test results, recording and reporting of the data under the project, overcoming initial hesitancy from the participants to take the Ag-RDT, need/demand for expanding the number of sites from those planned initially and refusal to undergo the Ag-RDT tests in a small number of enrolled persons due to perceived fear and stigma arising out of positive Ag-RDT test result.

Table 5: Lessons learnt/challenges encountered by the health care providers while implementing antigen RDTs pilot project in Jordan.

Domain	Lessons learned/Challenge (if any)
Identification of eligible population	Staff Challenges in excluding symptomatic individuals with symptoms duration over seven days from taking the Ag-RDTs, especially when the participant voluntarily seeks self-testing to learn about it and to see the results on the spot.
Obtaining informed consent	No challenges were encountered; the acceptability of the tests was very high
Conducting the test	No challenges were encountered. Community health workers faced no challenges getting the samples or performing the Ag-RDT test. Especially since nasal swabs used in Jordan were more accessible to perform and less painful than nasopharyngeal swabs, as noted by health workers and participants.
Acceptability of positive/negative results	There were concerns from the participants about the positive test results being known to ‘others’, especially in camps. This issue was addressed by assuring the privacy and confidentiality of the test results. Following these two measures, community health workers did not observe any other challenges regarding the acceptability of positive or negative test results.
Referral for rt-PCR testing	Challenges in referring participants eligible for rt-PCR testing to the related labs, especially among camps and Informal Tented Settlements due to mobility and financial constraints compared to participants visiting the health facilities where rt-PCR kits and professional staffs are readily available. In addition, following up on the rt-PCR results was significantly challenging as it required contacting every participant and obtaining their results.
Supply chain management issues of antigen RDTs or ancillary items	No challenges were encountered, and community health workers did not face any difficulties in the management of the supply chain of the Ag-RDT tests or the ancillary items related to personal protective equipment such as face shields, gloves, masks, disposal of wastes etc..,
Recording and reporting	Initially, there were challenges in recording the demographic and clinical characteristics directly into the KOBO app when conducting the Ag-RDTs. Therefore, data were first recorded in a logbook and then entered into the KOBO application. However, this method doubled the efforts for recording.
Overcoming initial hesitancy from participants to take the tests	On offering the Ag-RDT tests, many initially refused to take the tests. However, on-spot educational messages on the importance of ruling out COVID-19 and mitigating the fear of pain and discomfort from the test by informing that the RDTs in Jordan are Nasal and therefore cause less pain and discomfort improved the uptake of the test.
Need/demand for expanding the project to other sites	The CHWs needed to include more health facilities in other governorates than those envisaged initially due to a low number of persons with COVID-19 symptoms and the demand for expanding the Ag-RDT testing services in different areas by the public health authorities.
Mitigating communication challenges with non-Arab immigrants	The presence of community health workers of non-Arab nationalities was beneficial for delivering information directly and clearly in places where Asian immigrants multiply, especially in industrial cities.
Refusal to undergo Ag-RDTs by a few eligible persons.	The most common reasons for refusing the RDTs were fear of pain and discomfort, having recently undergone the test, or fear of stigma and isolation. In addition, some daily wage workers feared losing their work if employers knew about their positive test results, conspiracy theory, and belief that COVID-19 is over. CHWs had observed that refusals were more in the camps and Informal Tent Settlements than in hospitals and health centers.

This is one of the first studies describing the feasibility, uptake, and results of the Ag-RDT tests among refugees and migrants from Jordan in the MENA region. The study has the following implications for policy and practice regarding using ag-RDTs in this context.

6.1 Feasability and Uptake

First, Ag-RDTs were introduced at 17 of the originally planned 19 sites catering to refugees and migrants. In addition, the Ag-RDT testing services were expanded to 29 other locations, including two additional Governates (Ma’an and Ajloun), guided by the high demand for these services at these places due to more refugees and migrants in these Governorates. Most of the tests were conducted by trained CHWs who experienced minimal or no difficulty in performing the tests. All these indicate the excellent feasibility of Ag-RDTs among these populations in Jordan. In addition, the proportion of consented participants at all sites was >99%, indicating a good uptake of the tests. These findings add to the global evidence on the good feasibility of using Ag-RDTs for controlling the COVID-19 pandemic [22,23]

6.2 Positivity Rates

The overall test positivity was very low (0.6%), indicating the low prevalence of COVID-19 infection at the community level. This is consistent with Jordan’s Ministry of Health, which stopped publishing data on COVID-19 infections in September 2022 due to the very low positivity rate[21]. However, as found in this pilot project, there appear to be a few sites and population sub-groups where the test positivity was relatively higher such as the TB clinic at Mafraq, Amman PHC, those with severe COVID-19 symptoms, those with a history of contact with a COVID-19 infected person, those with recent travel history and health care workers. This indicates small pockets of COVID-19 transmission in some sites/population sub-groups. Therefore, there is a need to maintain high surveillance levels to prevent further infection transmission from these sites/population sub-groups. Also, two doses or more vaccination rates among this population were about 70%, which could also be responsible for the low prevalence of infection in this setting. The nationally reported vaccination rate in Jordan of 2 doses or more among all populations during our implementation period was around 41.5%[24]. In this pilot project, the test positivity rates were not significantly different in those unvaccinated/partially vaccinated persons than those who self-reported two or more vaccination doses.

6.3 Performance of Ag-RDTs

Based on the data available in this pilot project (though not ideal), it appeared that the test had a high specificity (98.5%), relatively low sensitivity (72%), very high negative predictive value (>98%), and low overall positive predictive value (57%) when compared to the manufacturer's reported specificity (99.8%) and sensitivity (98.1%)[25]. Such differences between manufacturer values and the actual in-field values have also been found in other studies[26]. However, this project was implemented in Jordan during a low prevalence COVID-19 period, which could have affected the accuracy of Ag-RDTs[27]. In addition, the accuracy of Ag-RDTs depends on the time from onset of symptoms, the concentration of virus in the specimen, the quality and processing of the sample collected from a person, and the precise formulation of the reagents in the test kits[28]. Therefore, more vigilance is needed in low-prevalence settings.

6.3.1 High Specificity and Negative predicive values

The high specificity (98.5%) and Negative predictive values (>98%) of the used Ag-RDTs in our project validate the reliability of Ag-RDTs in screening out negative COVID-19 persons. In comparison, the higher positivity rates among persons with severe COVID-19 Symptoms (4.2%) indicate the high reliability of Ag-RDTs in screening patients visiting different health facilities with COVID-19 symptoms. Therefore, embedding Ag-RDTs in COVID-19 testing strategies within national policies would benefit from the utility of Ag-RDTs.

6.4 Confirmatory PCRs Challenges

Importantly, confirmatory rt-PCR tests for those with positive Ag-RDT test results could be done only for 15% of those with positive results due to the lack of an efficient sample collection and transportation system. Persons with positive Ag-RDT test results were expected to visit the rt-PCR sites and provide the samples in person. However, due to challenges in private transportation, fear of using public transportation, and the unwillingness of the Ag-RDT-positive persons to visit the rt-PCR sites, confirmatory rt-PCR testing rates were very low. Studies have reported similar challenges in performing confirmatory PCR tests following Ag-RDTs, leading to low usage of PCRs to validate the Ag-RDTs result [29,30]. Therefore, in future projects, linking eligible persons for confirmatory rt-PCR testing needs to be built in through a combination of a specimen collection and transportation system and/or the safe transportation of persons with Ag-RDT positive results to the rt-PCR testing sites. In addition, although about 8% of those with negative antigen-RDT test results had undergone the rt-PCR test, for most of them, the rt-PCR test results were unavailable as rt-PCR results need hours/days to occur when performed in local governmental health facilities, making it more challenging for CHWs to follow-up on them for every participant. Therefore, given that rt- PCR tests are the only recommended COVID-19 tests in Jordan[31], clinical and public health decisions may highly consider the utility of Ag-RDTs results in screening in and out COVID-19 among these populations, whether in conjunction with rt-PCR or as a stand-alone test.

6.5 Role of CHWs

Lastly, the success of this pilot project in demonstrating high levels of feasibility and uptake can be attributed to the excellent rapport that the community health workers have established with the target populations for delivering the TB and HIV services under the Global Fund’s MER project. Some initial hesitancy in the uptake of the Ag-RDT was overcome by direct one-to-one information, education, and counselling on the benefits of testing. This helped remove the fear/misconceptions of a positive test result and improved the uptake of tests during the implementation. This aspect must be incorporated into similar projects implemented in this or other similar settings.

6.6 Strengths and Limitations

The major strength of the pilot project is that it was implemented under routine programmatic conditions through CHWs, with relatively sound data recording, supervision, and monitoring systems. Therefore, the pilot project’s experiences reflected through this operational research study on feasibility, uptake, and COVID-19 positivity rates are reliable and reflective of the ground-level realities in these populations. The study's major limitations were a) the pilot project was implemented at a very low community-level transmission of COVID-19 infection period and mostly in geographical areas and sites where the IOM was previously involved in implementing TB and HIV services. Therefore, the study findings may or may not be generalizable to other periods with different COVID-19 transmission dynamics or in similar populations not covered by the IOM project; b) the data on lessons learnt/challenges for implementation were collected during supervisory visits by project coordinators. Therefore, the information gathered could be biased if the respondents were uncomfortable sharing information about all the challenges with their supervisors; c) while implementing the project activities, emphasis on repeating the Ag-RDT test instead of rt-PCR tests for those with a positive test result was missed. As a result, none with positive test results appeared to have undergone the repeat Ag-RDT test. Therefore, whether repeat Ag-RDT testing is feasible and an acceptable alternative to the rt-PCR test remains unknown from this pilot project.

This project in Jordan showed that it is feasible to use Ag-RDT tests among refugees and migrants, and the uptake of the test is high. The overall test positivity was very low (0.6%). However, there were certain population sub-groups in which the test positivity was as high as 4%, indicating that the threat of COVID-19 transmission persists, and the health system preparedness and preventive measures need to continue. The utility of Ag-RDTs in screening out COVID-19 infection in asymptomatic people and screening in severely symptomatic people would highly recommend directing decisions on clinical management and public health to rely on Ag-RDT results whether in conjunction with rt-PCR results or as a stand-alone measure to screen in and out patients with COVID-19 specifically among refugees and migrants populations especially considering the major challenges in linking persons with positive Ag-RDT test results to confirmatory rt-PCR test, when indicated.

MENA Middle East North Africa

Ag-RDTs Antigen Rapid Diagnostic Tests

rt-PCR Molecular reverse transcriptase polymerase chain reaction

IOM International Organization for Migration

FIND Foundation for Innovative New Diagnostics

MER Global Fund’s Middle East Response

CHWs Community Health Workers

PHCs Primary health care centers

TB Tuberculosis

Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Jordan University of Science and Technology – Institutional Review Board in Jordan (Ref.: 45/152/2022) on 25 October 2022.

Informed Consent Statement: All subjects gave their written informed consent for inclusion in the Ag-RDTs project.

Data Availability Statement: The datasets generated and/or analysed during the current study are not publicly available due to data protection and privacy policies following the UN Migration Agency (IOM) standards but are available from the corresponding author on reasonable request.

Competing Interest

The authors declare that they have no competing interests

Funding: This project was funded by the Foundation for Innovative New Diagnostics (FIND) to IOM with an agreement and IOM number ID: [JO10P0520/MP.0308]. Article processing charges are also funded by [FIND].

Author Contributions: Conceptualization, NW, SSS, KK and HA; Methodology, NW, SSN, HA, MA; Data Curation, HG, MN, SSN and MA Writing – Original Draft Preparation, HG, MN and SSN; Writing – Review & Editing, SSN, MN, HA, MA, SSS, KK and NW; Supervision, NW, HGSSN and MA; Funding Acquisition, SSS and KK.

(SSS=Sanjay, Sarin. SSN=Srinath, Satyanarayana)

Acknowledgments: Grace Javier and Noor ABZADOUGH, project administration, Christopher TOGARA, procurement and supply management, Nick BANKS, Information Technology FIND, All CHWs.

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No competing interests reported.

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Foot Note: Additional file 1: Written Consent Form – English (Arabic Translation is Available)

Feasibility, uptake, and performance of COVID-19 rapid antigen diagnostic tests among refugees and migrants: Finding from secondary analysis of data from a pilot project in Jordan

Status:

Version 1

Abstract

Figures

Introduction

1.1 The COVID-19 Pandemic

1.2 Introducing Antigen Rapid Diagnostic Tests (Ag-RDTs)

1.2.1 Ag-RDTs’ Implementation Gaps

1.3 Response – Ag-RDTs Implementation Project

1.1 Project Objectives

Materials and Methods

2.1 Study Design

2.2 The Ag-RDTs Project Implementation in Jordan

2.2.1 Country Setting

2.2.2 Project Setting

2.3 Eligibility Criteria

2.4 Recording and Reporting Data

2.4.1 Data Monitoring

3.5 Study Population and Study Period

3.6 Data Variables

3.7 Data Analysis and Interpretation

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1