0 Title: Cost analysis of genital inflammation screening as a predictor of sexually transmitted infections and bacterial vaginosis in women: evidence from the GIFT study in Madagascar, South Africa, and Zimbabwe Authors: Elise Smith1*, Aina Harimanana2, Tinashe Mwaturura3,4,Vaomalala Raharimanga2, Theodora Mayouya Gamana2, Katherine Gill5, Emma Harding-Esch6, Tania Crucitti2, Lindi Masson7,8, Jo-Ann Passmore7,9 and Edina Sinanovic1 OriginalPaper 1 1 2018 12905 1Health Economics Unit, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; 2Institut Pasteur de Madagascar, Antananarivo, Madagascar, 3Organization for Public Health Interventions and Development, Harare, Zimbabwe; 4The Biomedical Research and Training Institute, Harare, Zimbabwe; 5Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; 6London School of Hygiene & Tropical Medicine, London, England; 7Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa; 8 Women’s, Children’s and Adolescents’ Health and Disease Elimination Programs, Life Sciences Discipline, Burnet Institute, Melbourne, VIC, Australia; 9National Health Laboratory Service, Johannesburg, South Africa; *Corresponding author. Email address: elisevdw189@gmail.com Abstract Background Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are significant public health issues, particularly in sub-Saharan Africa, and are associated with genital inflammation and increased HIV acquisition risk. A substantial proportion of these infections are asymptomatic, limiting the effectiveness of a syndromic approach. The Genital InFlammation Test (GIFT), a rapid point-of-care (POC) test, was developed to detect increases in inflammatory biomarkers associated with genital inflammation. The first-in-field prototype of the GIFT device was evaluated in a multicenter observational study conducted in South Africa, Zimbabwe, and Madagascar. While previous cost estimates for a hypothetical GIFT prototype exist for South Africa, this study provides an updated, real-world cost analysis of implementing GIFT screening within routine family planning services in South Africa and extends this analysis to Madagascar and Zimbabwe. Methods A provider-perspective, combining a top-down and bottom-up costing approach, was conducted at device evaluation observational study sites in Madagascar, South Africa, and Zimbabwe. Economic costs, including capital and recurrent expenditures, were collected through facility records, interviews, and self-reported provider timesheets to determine the incremental cost of integrating GIFT screening into family planning consultations. Research-related costs were excluded. A probabilistic sensitivity analysis using Monte Carlo simulation was performed to address parameter uncertainty, particularly around GIFT’s estimated market price of US$5.00. Results The incremental cost per woman screened with GIFT was estimated to be US $6.46 (95% CI: US $1.98 – US $12.22) in Madagascar, US $9.05 (95% CI: US $3.78 – US $15.83) in South Africa, and US $8.28 (95% CI: US $3.04 – US $16.52) in Zimbabwe. Recurrent costs (personnel, supplies, and overheads) constituted more than 98% of this cost, with the GIFT device being the primary cost driver. Conclusions This analysis suggests that the affordability and potential scale-up of GIFT and other novel POC screening tools will depend heavily on their final market price. The findings provide critical economic evidence to inform the broader adoption of GIFT into routine practice, including cost-effectiveness, affordability, and optimal strategies for its integration into sexual and reproductive healthcare services in low- and middle-income countries. Key words (3 to 10): Sexually transmitted infections Bacterial vaginosis Screening Genital inflammation Point-of-care testing Cost analysis Women's health Sub-Saharan Africa Introduction Sexually transmitted infections (STIs) remain a public health concern globally, with the most recent evidence from the World Health Organization (WHO) estimating that approximately one million new infections of the four most prevalent curable STIs, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and syphilis are acquired worldwide daily (1) Bacterial vaginosis (BV) is a common vaginal condition, affecting approximately one in four women of reproductive age. It is characterized by disruption of the normal vaginal microbiome, with a reduction in protective lactobacilli and an overgrowth of anaerobic bacteria. This imbalance may cause symptoms such as abnormal discharge and odor in some women, while others remain asymptomatic (2) A substantial proportion of both STIs and BV present without symptoms, especially in women and girls. When symptoms do occur, they are often non-specific and may not be perceived as abnormal, complicating case detection and clinical management (3) WHO has set ambitious targets aimed at reducing the global incidence of STIs by 2030, emphasizing the need to scale-up prevention and control measures, particularly in sub-Saharan Africa, which bears the highest burden worldwide(1) Progress towards these goals, however, remains challenging, in part due to limited diagnostic capacity in many low- and middle-income countries (LMICs). In addition, these targets do not encompass BV, despite its substantial global prevalence and comparable adverse effects on reproductive health outcomes to those of STIs (2). In settings where syndromic management remains the standard of care its limitations are significant: it has low predictive value for discharge-causing STIs such as CT, NG, TV and for BV and it is unable to identify asymptomatic infections.(3) A recent meta-analysis estimated that 61% of CT, 53% of NG and 57% of TV infections in women from LMICs are asymptomatic, with even higher proportions among women in Africa (69%, 67%, and 65%, respectively) (4). Estimates for asymptomatic BV range from 47% to 50% in LMICs, while studies in high income settings have found it to be above 80% (5–8). Both STIs and BV are known to induce genital inflammation in women, regardless of symptoms (9, 10). Genital inflammation, in turn, is strongly associated with increased risk of HIV acquisition and adverse birth outcomes(11, 12) This is particularly relevant in sub-Saharan Africa, where women are disproportionately affected by curable STIs and a substantial proportion of new HIV infections occur in women(3, 13) However, progress in developing point-of-care (POC) rapid diagnostics for CT, NG, TV and BV that fulfil WHO’s REASSURED criteria (including being affordable, rapid, equipment-free and deliverable to end-users) has been limited, leaving a critical gap in effective disease management(14, 15) Affordable diagnostic tools capable of delivering same-day results remain a pressing research and program priority, as they are essential for enabling timely initiation of appropriate treatment and reducing onward transmission(16, 17) To address this need, Masson and colleagues developed the Genital InFlammation Test (GIFT). GIFT is a rapid POC lateral flow assay detecting inflammatory biomarkers interleukin (IL)-1α, IL-1β, and interferon-γ-induced protein (IP)-10 from vaginal swabs and producing results in 15 minutes (13). By identifying genital inflammation, GIFT could facilitate the identification of women with asymptomatic STIs and BV and at elevated risk of HIV acquisition to strengthen sexual and reproductive health outcomes in settings where syndromic management is the norm. The GIFT study, a multicenter observational study conducted in South Africa, Zimbabwe, and Madagascar, evaluated the first-in-field prototype of the GIFT device. Its primary objective was to assess the sensitivity and specificity of GIFT for detecting asymptomatic, discharge-causing STIs (CT, NG, TV, Mycoplasma genitalium (MG)) and BV in women aged 18–35 years accessing family planning services, using nucleic acid amplification tests (NAATs) and Nugent scoring as reference standards (13). A key objective of the larger GIFT study was to assess potential pathways for integration into family planning services, including a cost analysis of implementing GIFT screening in real-world clinical settings. An earlier study estimated the costs of GIFT screening for STIs and BV during family planning consultations in South Africa, based on a hypothetical prototype of the GIFT device that was still under development (18). Cost estimates were derived from three health facilities in Cape Town, including a government clinic, a non-governmental clinic, and a semi-private clinic. The incremental cost of incorporating GIFT screening for the detection of asymptomatic STIs and BV during family planning consultations was estimated between US $3.53 (government clinic) and US $5.32 (semi-private clinic) (2016 prices inflated to 2023). This included a device cost of US $0.30 based on manufacturer’s price estimates of the GIFT (18) The primary aim of this study was to provide an updated estimate of the incremental cost of GIFT screening (testing of individuals who do not show symptoms to identify infections early and prevent transmission and complications) for STIs and BV in a real-world implementation setting, including South Africa and extending this analysis to Madagascar and Zimbabwe, based on evidence from the multicenter clinical observational GIFT device accuracy study (13). Methods Study design A combined top-down and bottom-up costing approach was applied to estimate the incremental cost per woman, and per woman per year, screened for STIs and BV using GIFT as part of routine family planning services in the three study settings. Economic costs, including both capital and recurrent costs, were assessed from the provider perspective. All research-related study costs were excluded so that resource utilization reflects the most likely scenario of routine implementation of GIFT screening in a real-world setting. Study sites The GIFT study was conducted at three sites across the three countries. In Madagascar, the study site was the Centre Hospitalier Universitaire de Gynécologie et d’Obstétrique de Befelatanana, a government university hospital in Antananarivo where family planning services are provided in a dedicated outpatient ward of the hospital. The Desmond Tutu Health Foundation (DTHF) Masiphumelele Youth Centre, a non-profit, donor-funded research center in Cape Town, was South Africa’s study site. DTHF operates an on-site clinic where youth-friendly sexual and reproductive health (SRH) services, including STI management, are provided. Given that DTHF is a donor-funded clinic, to estimate costs that are more representative of a public health setting, cost and service utilization data on family planning services were obtained from the nearby government Masiphumelele clinic, a public health clinic offering integrated family planning and STI services. All data related to the clinical study were obtained from the DTHF clinical study site. In Zimbabwe, the study was conducted at the Spillhaus Family planning Centre, a public clinic in Harare offering integrated SRH services including family planning, STI management, HIV prevention and fertility services. Across all three countries and study sites, syndromic management of STIs and BV remains the standard of care. Data collection Cost and resource utilization data of family planning consultations were obtained from facility management at each of the health facilities using semi-structured interview tools. Time allocation of clinical personnel to family planning services was collected through self-reported timesheets over a two-week period per site. Similarly, information on the time and consumables required to conduct GIFT screening was collected using self-reported timesheets completed by GIFT study nurses at each study site. For the base-case analysis, the GIFT device was assigned a cost of US $5.00, reflecting the manufacturer’s current best estimate of a potential market price. Where data were unavailable from the study sites, publicly accessible data sources or comparable data from similar study contexts were utilized (Table 1). Data Analysis Data were analyzed using a costing model developed in Microsoft Excel 365. The total cost of family planning and incremental cost of GIFT screening were estimated at the facility level. The incremental cost of GIFT screening was divided by the total number of female patients attending the clinic in the 2023 fiscal year to estimate the incremental cost of GIFT screening per woman. The total cost per woman screened per year was calculated as the product of the incremental cost per woman screened and the number of family planning consultations per woman per year. All costs are presented in 2023 United States Dollars (US $). Costs were inflated to 2023 prices using locally published inflation data where required and converted to US $ using the published average annual exchange rate for each country for the period 1 January 2023 to 31 December 2023 (US $1 = Malagasy Ariary 4,454.62, US $1 = South African Rand 18.46, US $1 = Zimbabwean Dollar 3,680.52 (19–21) Measurement, valuation, and allocation of costs Capital cost items included buildings, equipment, furniture, and provider training, while recurrent cost items comprised personnel, supplies, and overheads. Table 1 outlines the approach used to measure, value, and allocate these costs to GIFT screening consultations. Capital cost utilization was measured using facility records and interviews with the GIFT study team, and valued using current replacement costs from facility data, market prices, or published sources. These costs were annualized using standard assumptions on useful life and a 3% discount rate (22). Recurrent cost utilization was primarily measured through self-reported timesheets and facility records. These costs were valued using government salary scales, market prices, and facility expenditure data. Indirect and shared resources were allocated to the GIFT screening consultation using top-down approaches: Building costs were allocated according to the proportion of space used for family planning consultations, further apportioned to GIFT screening based on the share of direct personnel time devoted to GIFT as a proportion of total family planning consultation time; Equipment, furniture, indirect personnel, and overhead and maintenance costs were allocated in proportion to family planning consultations as a share of total outpatient visits. In Madagascar, hospital-wide shared costs (including overheads and maintenance) were allocated to family planning consultations based on the proportion of these visits relative to the total hospital service volume. To ensure comparability between service types, inpatient days were converted to outpatient-equivalent visits using WHO-CHOICE conversion factors (23) Direct resources, including GIFT provider training, direct personnel time, and medical and non-medical supplies, were allocated directly to GIFT screening. Measurement Valuation Allocation to GIFT screening Cost category Method Data source Method Data source Method Allocation factor Capital cost items Buildings Square meters of space used for FP consultations Obtained from facilities Current replacement value (cost per m2) (24)* Top-down FP space as % of total facility space x GIFT screening personnel time as % of total direct personnel time for FP Useful life (20 years) (25) Discount rate (3%) (22, 26) Equipment (medical & non-medical) and furniture Items used for FP departments Obtained from facilities** Current replacement value Health facility; market prices Top-down Total FP consultations as % of total outpatient consultations x GIFT screening as % of total direct personnel time for FP Useful life (15 years for furniture, 5 years for equipment) (25) Discount rate (3%) (22, 26) Provider training Provider time GIFT clinical study team Total annual renumeration Government salary scales Bottom-up Fully allocated to GIFT screening Useful life (5 years) (25) Discount rate (3%) (22, 26) Recurrent cost items Indirect personnel Time spent on FP- related support activities Self-reported timesheets Total annual renumeration Government salary scales Top-down Total FP consultations as % of total outpatient consultations x GIFT screening as % of total direct personnel time for FP Direct personnel Time spent on GIFT screening per study participant¥ Self-reported timesheets Total annual renumeration Government salary scales Bottom-up Direct; based on reported utilization Medical and non-medical supplies Supplies used for to conduct a GIFT test Self-reported reports Unit prices Health facility; market prices Bottom-up Direct; based on reported utilization Overheads & maintenance Apportioned usage Obtained from facilities** Total annual expenditure Facilities Top-down Total FP consultations as % of total outpatient consultations x GIFT screening as % of total direct personnel time for FP Note: FP = family planning; GIFT = Genital InFlammation Test;

Table 1 Measurement, valuation, and allocation of costs to GIFT screening

*Source for the replacement value of the clinic in South Africa. In the absence of data for Madagascar and Zimbabwe, building costs were estimated by applying the proportion of building costs of total unit costs as in South Africa. ** In the absence of available data from the clinic in South Africa, information was sourced from Kairu et al. (2020) and adjusted to 2023 prices. ¥Excludes study-related activities such as explaining study procedures, obtaining consent, and collecting additional swabs. Sensitivity analysis Univariate sensitivity analysis was conducted to identify the most influential parameters on the results of the analysis. Model parameters were varied to ± 30% of the base-case scenario. Results from this analysis are presented by means of tornado plots. Uncertainty analysis Given the small sample of this study, significant uncertainty existed around the base-case point estimates and the generalizability thereof to other settings within the same country. Parameter uncertainty was characterized using probabilistic sensitivity analysis (PSA) via Monte Carlo simulation with 1,000 iterations. Gamma or uniform distributions were assigned to cost input parameters, while lognormal or uniform distributions were applied to resource utilization parameters. The limited sample size in this study, both in terms of the number of facilities and the number of personnel from whom time estimates were collected, precluded the statistical calculation of means and 95% confidence intervals (CIs) for cost model parameters based on observed data. Consequently, base-case cost parameters primarily reflect single-point estimates or simple averages derived from the available observations (e.g., time measurements) or data collected from the facilities. Where possible, upper, and lower bounds for model parameters were derived from minimum and maximum values based on observed data; in the absence of empirical bounds, a ± 30% variation around the base-case estimate was assumed to parameterize the PSA model (27). Results from the PSA are presented as 95% CIs around the base-case point estimates. Results Facility and resource utilization, which informed the allocation of shared resources to family planning and ultimately GIFT screening, is presented in Table 2. The proportion of family planning consultations relative to total outpatient visits varied substantially across sites, accounting for 16% in Madagascar, 12% in South Africa, and 88% in Zimbabwe. Across the three facilities, clinical personnel (nurses) spent 71%, 84% and 78% of their time on activities related to family planning services, respectively. In the base-case analysis, each participant was assumed to attend four family planning consultations per year, reflecting an average utilization pattern of one clinic visit every three months. The average time taken by nurses to perform a GIFT test (including explaining the test to the client, collecting the vaginal swab, mixing with buffer and applying it to the test device and reading and interpreting results) excluding research-specific activities and the 15-minute test incubation period, was 11.67 minutes across the three sites. This is slightly higher than the 10 minutes estimated by Kairu et al. (2022) (18). Due the small number of observations across study sites, the average time across observations from all three study sites was applied to the cost estimates for all sites. Incubation time of the GIFT device was excluded based on the assumption that clinical personnel would be able to carry out other routine family planning consultation tasks while waiting for test results. Incubation time for the GIFT device was excluded from the personnel time cost, based on the assumption that nurses could perform other routine family planning consultation tasks while awaiting test results. Madagascar South Africa Zimbabwe Point estimate (min - max) n Point estimate (min - max) n Point estimate (min - max) n Source Family planning (FP) Total FP consultations, per year 4 135 (2 895–5 376) 1 4 727 (3 309–6 145) 1 2 263 (1 584–2 942) 1 Facility records* Total number of outpatient visits per year 25 229 (17 660–32 798) 1 40 907 (28 635–53 179) 1 2 586 (1 810–3 362) 1 Facility records* Total number of inpatients days per year 56 565 (39 596–73 535) 1 n/a 1 n/a 1 Facility records* FP consultations as % of outpatient visits 16% 1 12% 1 88% 1 Calculated % of total direct personnel time spent on FP (of all routine tasks, excluding GIFT screening) 71% (65% − 77%) 2 84% (71% − 98%) 4 78% (71% − 81%) 4 Provider timesheets¥ Total FP consultations, per woman, per year 4 (2–6) 1 4 (2–6) 1 4 (2–6) 1 Model assumption** GIFT screening Average time per GIFT test performed (minutes)α 11.67 (9.00–17.00) (n = 6) Provider timesheets¥ n/a: Not applicable

Table 2 Facility and resource utilization

*Minimum and maximum values represent +/-30% of reported parameters. **Based on the cadence of common contraceptive method, uncertainty ranges present likely minimum and maximum number of consultations per year per type of contraceptive method. αDue the small number of observations across study sites, the average time represents the average observations from across the three study sites. Incubation time of the GIFT device is excluded based on the assumption that clinical personnel would be able to carry out other routine family planning consultation tasks while waiting for test results. ¥ Minimum and maximum values from data collected. Table 3 presents the base-case unit cost estimates and the 95% CIs from the PSA. The incremental cost per woman screened with GIFT was estimated to be US $6.46 (US $1.98 – US $12.22) in Madagascar, US $9.05 (US $3.78 – US $15.83) in South Africa and US $8.28 (US $3.04 – US $16.52) Zimbabwe. Recurrent costs accounted for more than 98% of total unit costs in all three countries, with capital costs comprising the remainder. The GIFT device is the primary driver of the incremental cost of GIFT screening at an estimated unit price of US $5.00 (77% in Madagascar, 55% in South Africa and 60% in Zimbabwe). To reflect current uncertainty, a price range between US $1.00 and US $10.00 was applied for the device (refer to Sensitivity Analysis). The second biggest cost driver was medical supplies in Madagascar (15%), direct personnel in South Africa (30%), and indirect personnel in Zimbabwe (19%). Differences in cost estimates between the three countries were driven by variations in price levels, particularly those related to human resources, as well as differences in the allocation factors of shared costs to family planning and, ultimately, to GIFT. In Zimbabwe, where 88% of facility costs were allocated to family planning the indirect staff costs attributed to GIFT were substantially higher than in the other countries. In contrast, in South Africa, where human resource costs were higher than in Madagascar and Zimbabwe, direct personnel costs were greater despite the same level of direct resource utilization being assumed for GIFT screening. For comparability, costs are also presented in international dollars in Supplementary Table 1. Madagascar South Africa Zimbabwe Madagascar South Africa Zimbabwe Incremental cost per woman screened with GIFT, US $ (95% CI) Incremental cost per woman screened with GIFT, per year, US $ (95% CI) Capital costs Buildings 0.07 (0.02–0.29) 0.10 (0.05–0.28) 0.09 (0.03–0.39) 0.29 (0.08–0.90) 0.41 (0.12–1.32) 0.38 (0.10–1.69) Equipment and furniture 0.003 (0.001–0.007) 0.001 (0.0004–0.002) 0.05 (0.02–0.12) 0.01 (0.007–0.02) 0.003 (0.001–0.01) 0.19 (0.12–0.28) Procedure training 0.001 (0.0007–0.002) 0.01 (0.01–0.02) 0.01 (0.004–0.01) 0.004 (0.002–0.01) 0.05 (0.02–0.10) 0.03 (0.01–0.05) Total capital costs 0.08 (0.02–0.29) 0.12 (0.06–0.30) 0.15 (0.06–0.52) 0.31 (0.09–0.93) 0.47 (0.13–1.42) 0.59 (0.23–2.02) Recurrent costs Indirect personnel 0.08 (0.04–0.19) 0.26 (0.14–0.60) 1.57 (0.87–3.80) 0.31 (0.23–0.42) 1.04 (0.34–3.04) 6.24 (4.70–8.66) Direct personnel 0.32 (0.22–0.44) 2.67 (1.87–3.55) 0.49 (0.12–0.68) 1.26 (0.51–2.30) 10.68 (4.45–18.90) 1.94 (0.81–3.65) Medical supplies 0.99 (0.70–1.30) 0.99 (0.71–1.33) 0.99 (0.71–1.29) 3.95 (1.60– 7.10) 3.95 (1.64–7.16) 3.95 (1.68–7.15) GIFT device 5.00 (1.00–10.00) 5.00 (1.00–10.00) 5.00 (1.00–10.00) 20.00 (3.00–54.00) 20.00 (3.00–54.00) 20.00 (2.00–54.00) Overheads and maintenance 0.0005 (0.0002–0.001) 0.02 (0.01–0.04) 0.09 (0.04–0.24) 0.002 (0.001–0.003) 0.07 (0.02–0.22) 0.38 (0.24–0.57) Total recurrent costs 6.38 (1.96–11.92) 8.93 (3.72–15.53) 8.13 (2.98–16.00) 25.52 (5.33–63.82) 35.73 (9.46–83.31) 32.54 (9.44–74.03) Total costs 6.46 (1.98–12.22) 9.05 (3.78–15.83) 8.28 (3.04–16.52) 25.83 (5.42–64.75) 36.20 (9.60–84.73) 33.13 (9.67–74.03) Total cost, excluding GIFT device 1.46 (0.98–2.22) 4.05 (2.78–5.83) 3.28 (2.04–6.52) 5.83 (2.83–10.75) 16.20 (6.60–30.73) 13.13 (6.60–20.03)

Table 3 Unit cost results (2023 US $)

The incremental cost per woman screened per year, assuming routine screening at each of four family planning visits, was estimated to be US $25.83 (US $5.42 – US $64.75) in Madagascar, US $36.20 (US $9.60 – US $84.73) in South Africa and US $33.13 (US $9.67 – US $74.03) in Zimbabwe. Sensitivity analysis Figure 1 shows the results from the univariate sensitivity analysis where model parameters were varied with ± 30%. Across the three countries, a change in the GIFT device price resulted in the greatest change in unit cost, with a ± 30% change resulting in a ± 23%, ± 17% and ± 16% change in the incremental cost per woman screened in Madagascar, South Africa and Zimbabwe, respectively. The second most influential parameter was the time required to administer the GIFT device in Madagascar and South Africa, and the number of family planning consultants per woman, per year in Zimbabwe. The inverse relationship between the number of family planning consultations per woman per year and the cost of GIFT screening suggests that economies of scale could be realized by distributing fixed costs across a larger number of services, albeit relatively modest.

Fig. 1 Univariate sensitivity analysis results

Note FP = family planning GIFT = Genital InFlammation Test; Across countries, the GIFT device price had the greatest impact on unit cost; a ± 30% change led to ± 23%, ± 17%, and ± 16% changes in incremental cost per woman screened in Madagascar, South Africa, and Zimbabwe, respectively. The next most influential parameters were administration time (Madagascar, South Africa) and the number of FP visits per woman per year (Zimbabwe). Discussion This study provides a multi-country cost analysis of implementing GIFT, a rapid POC test for genital inflammation, or other similar tests, as a screening tool within routine family planning services in Madagascar, South Africa, and Zimbabwe. The use of empirical data from three distinct LMICs settings enhances the relevance of the findings for similar contexts. The incorporation of PSA allows for the quantification of uncertainty around point estimates, reflecting the inherent variability in cost parameters, especially given the small sample size of health facilities. The PSA results indicate a wide range of unit costs, largely attributable to the limited number of facilities sampled and uncertainty regarding the future market price of the GIFT device. As the device cost is the main driver of total implementation costs in our analysis, the overall affordability and scalability of GIFT screening will depend largely on its eventual market price; a critical consideration for implementation in LMIC settings. In the base case analysis, the device price was assumed to be US $5.00. However, the final market price will ultimately depend on the device’s components and where they are manufactured. Excluding the cost of the device, estimated screening costs varied from US $1.46 (US $0.98 – US $2.22) in Madagascar, US $4.05 (US $2.78 – US $5.83) in South Africa, and US $3.28 (US $2.04 – US $6.52) in Zimbabwe. The estimates for South Africa are slightly higher than the inflation-adjusted results reported by Kairu et al. (2022) for a government clinic (US $3.23, excluding device price), although they fall within the uncertainty range of the present analysis (18). The observed differences are primarily attributable to variations in human resource utilization. Overall cost estimates, including the device, were higher in our analysis largely because of the increased device price assumed, based on more recent manufacturer estimates. The findings have implications for policy and future research as a unit price of US $5.00 for the GIFT device, and overall implementation cost of US $6.46 in Madagascar, US $9.05 in South Africa and US $8.28 in Zimbabwe, may present an affordability challenge. Evidence on the costs of STI screening using POC tests in LMICs, including in Sub-Saharan Africa, remains limited and largely focused on HIV and syphilis. This is likely due to the lack of affordable and effective POC diagnostic tests for other STIs, including CT, TV and NG, and prevailing guidance to use syndromic management in these settings. To our knowledge, no published data currently exist on the cost of CT, NG, or TV screening using rapid POC tests in Africa or other LMICs. For context, a systematic review estimated the mean cost of facility-based HIV testing using rapid POC tests in Sub-Saharan Africa at US$19.63 per person tested (including post-test counselling), although self-testing approaches have achieved lower costs (US$12.75 per person tested) (28). Facility-based antenatal syphilis screening using rapid POC tests has been estimated at approximately US$1.00–4.00 per woman screened, with staff time and supplies, including the device itself, typically costing less than US$1.00, constituting the main cost drivers. When considering scale-up, screening or testing volumes are an important consideration, as higher volumes allow for economies of scale by spreading fixed costs such as training, start-up activities, facility operations, program supervision, and quality assurance, over a larger number of tests (29–38). Overall, these findings suggest that GIFT screening compares favorably with facility-based HIV testing and self-testing, though generally higher than antenatal syphilis screening. If device costs can be reduced and economies of scale achieved through scaled-up implementation, GIFT screening could represent an economically viable and feasible STI screening strategy in LMICs, with the potential to improve early detection and sexual and reproductive health outcomes. However, these cost considerations, must be interpreted alongside evidence of the device’s effectiveness and subsequent impact on health outcomes. Limitations This study has several limitations. First, data were collected from a single facility per country, which may not be representative of all public health facilities, limiting generalizability. Second, time allocation data relied on self-reported timesheets, which are subject to recall or reporting bias. Third, the US $5.00 cost of the GIFT device is a manufacturer’s estimate, and the final market price could differ, substantially impacting overall and relative costs. Fourth, where facility-specific data were unavailable, costs were imputed using published sources or proportional estimates from other sites, such as building costs in Madagascar and Zimbabwe, which may not fully reflect local conditions. Finally, this analysis did not include the costs of confirmatory testing for STIs and BV, which would form a key component of the management of STIs and BV following positive GIFT test results. Conclusion This cost analysis demonstrates that incorporating GIFT screening into routine family planning services costs between US $6.46 and US $9.05 per test across settings in Madagascar, South Africa, and Zimbabwe. The cost of the device itself is the predominant cost driver, underscoring that the affordability of this novel POC technology will be central to its potential for widespread adoption. These findings provide essential evidence for the broader economic evaluation of implementing GIFT as a screening tool for STIs and BV in LMICs. While this study provides a quantitative assessment of the economic costs associated with GIFT implementation, a comprehensive policy and research perspective requires integrating these cost data with evidence on clinical effectiveness from the ongoing GIFT study. Emerging results on cost-effectiveness, affordability, and acceptability will be essential to guide the design of implementation strategies, such as optimizing screening frequency or targeting high-risk sub-populations, to maximize health benefits within existing resource constraints. Abbreviations AGYW Adolescent Girls and Young Women BV Bacterial Vaginosis CI Confidence Interval CT Chlamydia trachomatis DTHF Desmond Tutu Health Foundation FP Family Planning GIFT Genital InFlammation Test HIV Human Immunodeficiency Virus IL 1α / IL–1β–Interleukin–1 alpha / Interleukin–1 beta IP 10–Interferon gamma–induced protein 10 LMICs Low–and Middle–Income Countries MG Mycoplasma genitalium MGA Malagasy Ariary (currency) NAATs Nucleic Acid Amplification Tests NG Neisseria gonorrhoeae POC Point–of–Care PSA Probabilistic Sensitivity Analysis SRH Sexual and Reproductive Health STI Sexually Transmitted Infection TV Trichomonas vaginalis US$ United States Dollar WHO World Health Organization Ethics approval and consent to participate Ethical approval for this study was granted by the following research ethics committees: Human Research Ethics Committee, University of Cape Town (UCT) (Ref: 366/2022 and 173/2023), Observation/Intervention Research Ethics Committee, London School of Hygiene & Tropical Medicine (Ref: 28046), Ministère de la Santé Publique (Ref: 64-MSANP/SG/AMM/CNPN/CERMB), Research Council of Zimbabwe (Ref: 04768), City Health, City of Cape Town (Ref: 9870). The study was conducted in compliance with the Declaration of Helsinki (2013). Informed consent for the costing study was waived as the research involved the analysis of fully de-identified data with minimal risk to participants. Consent for publication Not applicable Data AvailabilityResearch generated in this study is available upon reasonable request from the corresponding author. Competing InterestsJo-Ann Passmore and Lindi Masson are co-inventors on a patent related to the combination of three inflammatory biomarkers (IL-1α, IL-1β, and IP-10) used in the GIFT diagnostic assay for genital inflammation (South African Patent No. 2016/03606 and European Patent No. 14809984.9). Both inventors declare that while this intellectual property is related to the biomarker combination evaluated in the current study, neither they nor their institutions currently receive personal financial benefits from the patent. Funding This research was funded under the European and Developing Countries Clinical Trials Partnership (EDCTP) (grant number RIA2020I-3297). Author ContributionE. Smith (ESm) drafted the main manuscript and, together with E. Sinanovic (ESi), led the conceptualisation and design of the study. AH, TM, VR, TMG, and KG supported and facilitated data collection. ESm conducted the data analysis. ESi, EHE, KG, LM, and JAP contributed to the interpretation of the findings. All authors reviewed and approved the final manuscript. Acknowledgements Not applicable Electronic Supplementary Material Below is the link to the electronic supplementary material Supplementary Material 1 References 1. World Health Organization. Global progress report on HIV, viral hepatitis and sexually transmitted infections. 2021: accountability for the global health sector strategies 2016–2021: actions for impact [Internet]. 2021 [cited 2025 Aug 31]. Available from: https://iris.who.int/handle/10665/341412 2. 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