Cost-effectiveness of outdoor residual spraying, insecticide-treated nets, and their combination for zoonotic malaria control in Sabah, Malaysia: a comparative analysis

Abstract

Background

Following the elimination of human malaria, Malaysia has experienced an increasing burden of zoonotic Plasmodium knowlesi malaria, particularly in Sabah. Evidence on the cost-effectiveness of vector control interventions is needed to inform policy decisions and optimise resource allocation. This study assessed the cost-effectiveness of Outdoor Residual Spraying (ORS), Long-Lasting Insecticidal Nets (LLINs), and their combined use for controlling P. knowlesi malaria in Sabah, Malaysian Borneo.

Methods

A cost-effectiveness analysis was conducted from the healthcare provider perspective over a one-year time horizon in three high-endemic districts: Keningau (LLINs), Ranau (ORS), and Kota Marudu (ORS + LLINs). Capital and recurrent components, were estimated using an ingredient-based costing approach. Effectiveness was measured as the number of P. knowlesi cases averted based on routine surveillance data. Incremental cost-effectiveness ratios (ICERs) were calculated relative to a no-intervention scenario, defined as health promotion activities without vector control. One-way sensitivity analyses assessed uncertainty in key parameters. All costs were reported in Malaysian Ringgit (MYR) and adjusted to 2025 values.

Results

Annual provider costs ranged from MYR 3912.92 (no intervention) to MYR 39,764.14 (ORS + LLINs). ORS was associated with the highest number of cases averted (n = 13) and the lowest ICER (MYR 2046 per case averted; approximately USD 470). LLINs and the combined strategy were associated with fewer cases averted and higher ICERs. ORS consistently demonstrated the most favourable cost-effectiveness profile across all sensitivity analyses.

Conclusion

ORS demonstrated the most favourable cost-effectiveness profile under the observed programme conditions for controlling P. knowlesi malaria in Sabah. A stratified approach prioritising ORS, with targeted use of LLINs among high-risk populations, may represent an economically efficient strategy in resource-limited settings.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12936-026-05934-9.

Background

Malaria remains one of the most significant global public health challenges, imposing substantial morbidity, mortality, and socioeconomic burden worldwide [1–5]. In 2023, an estimated 263 million malaria cases were reported globally, representing an increase compared with the previous year and signalling a concerning reversal in progress toward elimination [1, 2, 5].

Although malaria-related deaths have declined slightly, approximately 597,000 deaths continue to occur annually, highlighting persistent gaps in prevention, diagnosis, and treatment. This stagnation threatens the achievement of the World Health Organization (WHO) Global Technical Strategy (GTS) targets, which call for at least a 90% reduction in malaria incidence and mortality by 2030 [1, 2, 5, 6]. The continued burden of malaria, particularly in regions with limited healthcare infrastructure, underscores the urgent need for control strategies that are both effective and efficiently deployed [1, 8–13]

Compounding these challenges, the emergence of new malaria transmission dynamics, including zoonotic malaria, has further complicated conventional malaria control efforts and necessitates targeted, evidence-based solutions. Malaysia represents a notable success in having eliminated human-only malaria particularly caused by Plasmodium falciparum and Plasmodium vivax [1, 2, 5, 14–17].

However, this achievement is increasingly overshadowed by the persistent and rising burden of zoonotic malaria due to Plasmodium knowlesi. In 2023, global P. knowlesi cases increased by nearly 19%, with Malaysia accounting for over 87% of the global burden and reporting all associated indigenous deaths [1, 2, 5, 14–17].

Within Malaysia, Sabah in Malaysian Borneo remains the epicentre of P. knowlesi transmission, contributing approximately 80% of the national caseload [2–5]. Unlike human malaria, P. knowlesi transmission involves a complex ecology cycle that includes forest-dwelling, outdoor-biting mosquito vectors and non-human primate reservoirs [14–17].

This unique transmission ecology reduces the effectiveness of conventional vector control measures, such as indoor residual spraying (IRS) and insecticide-treated nets (ITNs), which are primarily designed to interrupt indoor transmission. Consequently, there is a critical need to identify, evaluate, and prioritise interventions specifically adapted to address outdoor and peri-domestic transmission associated with zoonotic malaria [2, 14, 15].

The rising burden of P. knowlesi also occurs in the context of constrained malaria financing, with available resources consistently falling short of both global and national needs [1, 5, 9]. In such a scenario, prioritising interventions that are not only effective but also economically efficient becomes a priority. While substantial cost-effectiveness evidence exists for ITNs and IRS targeting human malaria in Africa and the Greater Mekong Subregion, evidence for interventions tailored to zoonotic malaria remains limited [19–22].

In particular, there is a lack of local, healthcare provider-perspective economic evaluations for Integrated Vector Management (IVM) strategies, such as targeted Outdoor Residual Spraying (ORS), Long-Lasting Insecticidal Nets/Insecticidal Treated Net (LLIN/ITN), and their combination, which are specifically designed to mitigate outdoor and peri-domestic transmission [1, 5–13, 22].

This evidence gap constrains the ability of policymakers and programme managers to make informed resource allocation decisions and may impede effective control and eventual elimination of P. knowlesi in Malaysia and other endemic settings. To address this gap, a comparative cost-effectiveness analysis was conducted from the healthcare provider perspective in Sabah, Malaysia, evaluating three intervention strategies: targeted ORS, distribution of LLINs/ITNs, and a combined ORS–LLIN/ITN approach.

The study aimed to: (i) estimate the total financial costs of each intervention; (ii) assess their effectiveness in terms of P. knowlesi cases averted; (iii) calculate incremental cost-effectiveness ratios (ICERs) relative to current practice; and (iv) evaluate the robustness of the findings through one-way sensitivity analyses of key parameters.

Methods

Study design and setting

This study employed a cross-sectional cost-effectiveness analysis conducted over 1 year, from January to December 2023, in Sabah, Malaysian Borneo. Sabah was selected due to its high burden of zoonotic malaria caused by P. knowlesi and the implementation of multiple vector control strategies under routine malaria control programme activities.

Three districts namely, Keningau, Ranau, and Kota Marudu were purposively selected as study sites based on two criteria: (i) a documented high incidence of zoonotic malaria and (ii) the implementation of distinct, stand-alone vector control interventions that allowed comparative evaluation. Each district represented a specific intervention strategy: Keningau implemented LLIN/ITN, Ranau implemented ORS, and Kota Marudu implemented a combined ORS and LLIN/ITN strategy.

Study population and sampling

The study population comprised premises and malaria control programmes within the three selected districts. A multi-stage sampling approach was used to select representative premises within each district. In the first stage, high-risk localities were identified in collaboration with the District Health Offices, based on routine malaria surveillance data.

In the second stage, premises within these localities were systematically sampled. A total of 420 premises were included, with 140 premises sampled from each district. The total population covered by the interventions in the sampled premises was enumerated for each district: 303 persons in Ranau (ORS district), 309 persons in Keningau (LLIN district), and 314 persons in Kota Marudu (ORS + LLIN district). These population data were used to calculate cost per person. These premises were used for both cost estimation and effectiveness assessment.

Inclusion and exclusion criteria

Premises located within the selected districts and covered by at least one of the evaluated malaria control interventions (ORS, LLIN/ITN, or a combination) were included. Premises not covered by any of the three interventions during the study period were excluded.

Description of vector control programmes

The three vector control interventions evaluated in this study were Outdoor Residual Spraying (ORS), Long-Lasting Insecticidal Nets/Insecticide-Treated Nets (LLIN/ITN), and a combined ORS and LLIN/ITN strategy. All interventions were implemented as part of routine malaria control activities by the Ministry of Health Malaysia between January and December 2023. Intervention delivery was conducted in selected high-risk localities within each district based on routine malaria surveillance data and programme prioritisation.

ORS involved the application of residual insecticides on outdoor surfaces of human dwellings and peri-domestic structures to target outdoor-biting mosquito vectors. LLIN/ITN involved the distribution of insecticide-treated bed nets to households for personal protection against mosquito bites. The combined strategy involved the implementation of both ORS and LLIN/ITN within the same district.

In Keningau district, LLIN/ITN distribution was implemented in Kampung Biah 1 and Kampung Biah 2. In Ranau district, ORS was implemented in Kampung Maringkan and Kampung Tampios, while in Kota Marudu district, the combined ORS and LLIN/ITN strategy was implemented in Kampung Sampir and Kampung Muhang.

A total of 420 premises were included across the three districts, with 140 premises selected in each district to ensure balanced representation for both cost estimation and effectiveness assessment.

The ORS intervention involved the application of residual insecticide to outdoor surfaces of human dwellings and peri-domestic structures, including walls, toilets, and small storage areas. Spraying coverage extended to surrounding vegetation, including trees within a radius of approximately five metres from the household, based on environmental exposure and transmission risk factors. ORS operations were conducted twice annually (every six months) as part of scheduled programme implementation.

The LLIN/ITN intervention involved the distribution of insecticide-treated bed nets to households based on household composition. Nets were allocated according to family structure, with individual (single-use) nets provided for unmarried individuals or children, and larger or multiple nets provided for family units. Follow-up monitoring activities were conducted approximately 6 months post-distribution to assess utilisation, condition, and retention of the nets.

Although detailed population-level coverage proportions were not consistently available across all districts, all intervention areas represented targeted high-risk localities identified through district malaria surveillance systems.

Data collection and analysis

Costing methods

Cost data were collected from the healthcare provider perspective and reported in Malaysian Ringgit (MYR), with 2025 as the reference price year to reflect updated programme expenditures and market prices. An ingredient-based costing approach was used to identify, quantify, and value all resources required for the implementation of each intervention.

For international comparability, selected cost and cost-effectiveness results were also converted into United States dollars (USD) using an average exchange rate of approximately 1 MYR = 0.23 USD, based on publicly available financial data [23].

Both capital and recurrent costs were included. Capital costs comprised assets and equipment with a unit value exceeding MYR 500, including equipment items used for vector control operations. Recurrent costs included personnel emoluments, insecticides, supplies and consumables, diagnostic tests, travel, training, monitoring and evaluation activities, as well as building and facility-related expenses, utilities, and administrative costs.

Building costs were included under recurrent costs rather than capital costs because all buildings were of a similar age, and some premises were rented. To standardise valuation, costs were estimated using the current rental price per square metre according to the Jabatan Kerja Raya (JKR) guidelines, rather than historical construction costs or annualised capital costs. This approach ensured that building costs reflected current operational expenses relevant to programme implementation [24].

Unit costs (cost per premises and cost per person) were calculated by dividing total programme costs by the number of premises (140 per district) and by the population covered in each district, respectively. These unit cost estimates were computed to facilitate comparison across interventions and with other settings.

A mixed costing methodology was applied. Step-down costing allocated shared and overhead costs across intervention activities, while activity-based costing (ABC) was captured directly attributable intervention resources [17–19]. Cost data were obtained from accounting, financial, and administrative records of the Ministry of Health Malaysia, including the Vector-Borne Disease (Malaria) Sector, the Sabah State Health Department (JKN Sabah), the Entomology Unit, and the respective District Health Offices. All cost components were compiled and analysed using a standardised Excel-based costing calculation template.

Effectiveness measurement

Intervention effectiveness was measured as the observed number of Plasmodium knowlesi malaria cases averted under routine programme conditions. Baseline zoonotic malaria occurrence was established using surveillance data from 2020–2021. For Ranau and Kota Marudu, baseline data were derived from the same localities prior to intervention implementation, while proxy baseline data were used for Keningau due to data availability constraints.

The number of cases averted was calculated as the difference between baseline case occurrence and the number of confirmed cases reported during the study period (January–December 2023). Malaria case data were obtained from multiple sources, including the e-vekpro surveillance system, e-notifikasi records, and medical records from district hospitals.

The analysis was based on 420 selected premises across three districts (140 premises per district), representing targeted high-risk localities identified through routine malaria surveillance systems. These premises formed the basis for both cost estimation and effectiveness assessment under each intervention strategy.

Given that interventions were implemented in different districts and localities, variations in baseline case occurrence, ecological conditions, vector density, and population characteristics may influence observed outcomes. Therefore, effectiveness estimates should be interpreted as descriptive programme outcomes rather than causal effects attributable solely to the interventions.

In addition, the use of routine surveillance data does not allow adjustment for temporal trends or external factors such as climate variation, improvements in case detection, or behavioural changes within the population.

Comparable population denominator data were not consistently available across all intervention localities; therefore, effectiveness was primarily reported using absolute case counts and cases averted. This approach may limit comparability with studies reporting incidence rates or DALY-based outcomes. This pragmatic approach reflects real-world programme evaluation conditions, where complete epidemiological and population-level data may not always be available.

Cost-effectiveness analysis

A cost-effectiveness analysis conducted by comparing each intervention against a no-intervention baseline, defined as routine health promotion activities without preventive vector control, over a one-year time horizon (January–December 2023).

Capital assets with a useful life exceeding one year were annualised using a 5% discount rate to derive equivalent annual costs. Building costs, being based on rental rates per square meter, did not require further annualisation. Given the one-year timeframe, no additional discounting was applied to costs or outcomes.

Incremental cost-effectiveness ratios (ICERs) were calculated using the standard formula:

$$ICER=\left(\text{Cos}t\_\text{int}ervention-\text{Cos}t\_control\right)/\left(Effect\_\text{int}ervention-Effect\_control\right)$$

where effectiveness was defined as the number of Plasmodium knowlesi cases averted relative to the no-intervention baseline. The ICER represents the additional cost required to avert one additional malaria case compared to the baseline scenario. Results are presented as cost per P. knowlesi case averted.

Sensitivity analysis

A one-way sensitivity analysis was performed to assess the robustness of the primary cost-effectiveness findings. Key cost and effectiveness parameters for each intervention were varied across three scenarios:

1. Base-case scenario: parameters were set at observed or most likely values, representing standard programme implementation.

2. Best-case scenario: lower plausible values for cost parameters and higher plausible values for effectiveness, where applicable, representing the most favourable economic scenario.

3. Worst-case scenario: higher plausible values for cost parameters and lower plausible values for effectiveness, representing the least favourable economic scenario.

Parameter variation was applied to major cost components, including personnel emoluments, insecticide and bed net procurement, consumables, equipment, utilities, training, and administrative costs.

The resulting variation in total programme costs and incremental cost-effectiveness ratios (ICERs) was examined to evaluate the stability of intervention rankings across different assumptions.

Parameter ranges were defined based on plausible variation in programme costs and effectiveness observed across the study districts. Due to data limitations, probabilistic sensitivity analysis was not performed. All analyses were conducted using Microsoft Excel 2021.

Reporting guidelines

This economic evaluation was conducted and reported in accordance with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 statement to ensure transparent and complete reporting [25]. A completed CHEERS checklist is provided as Supplementary Material 1.

Results

The cost analysis

Table 1 presents the annual provider costs of vector control interventions for P. knowlesi in Sabah. Total programme costs varied substantially across interventions. The no-intervention baseline, representing routine health promotion without preventive vector control, incurred the lowest annual cost (MYR 3912.92; approximately USD 900). Among the evaluated interventions, the combined ORS + LLIN/ITN programme was the most expensive (MYR 39,764.14; approximately USD 9150), followed by ORS alone (MYR 30,507.17; approximately USD 7000) and LLIN/ITN alone (MYR 18,089.35; approximately USD 4160). Selected cost estimates are also presented in USD for international comparability.

Table 1.

Annual provider costs of vector control interventions for Plasmodium knowlesi in Sabah (MYR, 2025 prices)

Cost category	Cost component	Costing method	No intervention	ORS	LLIN	ORS + LLIN
Capital costs	Assets/Equipment/Vehicles (> RM500)	Step-down	31.01	31.01	32.93	26.81
Recurrent costs	Building	Step-down	839.45	839.45	839.34	1,180.77
	Utilities	Step-down	76.24	76.24	78.93	120.31
	Administrative	Step-down	62.32	62.32	29.51	97.12
	Training	Step-down	115.00	115.38	86.21	113.13
	Personnel (Emolument)	ABC	1392.57	3,028.23	2,575.69	2,498.34
	Consumables (Non-drug)	ABC	1396.33	1,920.14	1,298.92	2,192.52
	Commodities (Bed-nets/Insecticides)	ABC	–	24,434.40	12,923.82	33,535.14
	Laboratory tests	ABC	–	–	224.00	–
Total cost (MYR)			3912.92	30,507.17	18,089.35	39,764.14

ORS, Outdoor Residual Spraying; LLIN, Long-Lasting Insecticidal Net; ITN, Insecticide-Treated Net; ABC, Activity-Based Costing. Costs are reported in Malaysian Ringgit (MYR), 2025 prices (adjusted from 2023 expenditure data). Step-down costing was used to allocate shared/overhead costs; ABC was applied to directly attributable resources. "No Intervention" represents routine health promotion without preventive vector control. Exchange rate: 1 MYR = 0.23 USD (World Bank, 2025). Approximate USD equivalents: No intervention = USD 900; ORS = USD 7,017; LLIN = USD 4,161; ORS + LLIN = USD 9,146

Capital costs, including assets, equipment, and vehicles, accounted for a small proportion of total programme costs across all interventions. Recurrent costs, particularly personnel emoluments, consumables, and commodities such as bed nets and insecticides, constituted the majority of expenses. For example, insecticide and bed-net procurement represented the largest single cost component for ORS and LLIN interventions. Building and utility costs, administrative overheads, and training contributed moderately to total costs in Table 1.

Commodities (insecticides and bed nets) represented the largest cost component across all interventions, accounting for 80.1% of ORS costs, 71.4% of LLIN costs, and 84.3% of combined ORS + LLIN costs. Personnel emoluments contributed 9.9%, 14.2%, and 6.3% respectively. The remaining costs consisted of building, utilities, administration, training, consumables, and laboratory tests.

Unit cost estimates were calculated to facilitate comparison across interventions and with other settings. As presented in Table 2, the cost per premises ranged from MYR 129.21 (approximately USD 29.72) for LLIN in Keningau to MYR 284.03 (approximately USD 65.33) for the combined ORS + LLIN strategy in Kota Marudu. The cost per person ranged from MYR 58.54 (approximately USD 13.46) for LLIN to MYR 126.64 (approximately USD 29.13) for the combined strategy. The ORS intervention in Ranau had a cost per premises of MYR 217.91 (USD 50.12) and a cost per person of MYR 100.68 (USD 23.16). These unit cost estimates complement the total programme costs reported in Table 1 and provide a basis for cross-setting comparability.

Table 2.

Unit costs of vector control interventions for Plasmodium knowlesi in Sabah (MYR, 2025 prices)

Intervention	District	Premises (n)	Population (n)	Average household size	Cost per premises MYR	Cost per person MYR
ORS	Ranau	140	303	2.16	217.91	100.68
LLIN	Keningau	140	309	2.21	129.21	58.54
ORS + LLIN	Kota Marudu	140	314	2.24	284.03	126.64

Cost per premises was calculated by dividing total programme cost (from Table 1) by 140 premises per district. Cost per person was calculated by dividing total programme cost by the population covered in each district. Average household size is provided for contextual information. USD values are approximate and for international comparability only. Exchange rate: 1 MYR = 0.23 USD (World Bank, 2025). Approximate USD equivalents: ORS = USD 50.12 per premises, USD 23.16 per person; LLIN = USD 29.72 per premises, USD 13.46 per person; ORS + LLIN = USD 65.33 per premises, USD 29.13 per person

The effectiveness and cost-effectiveness analysis

The effectiveness and cost-effectiveness of the interventions are presented in Table 3.

Table 3.

Effectiveness and cost-effectiveness of vector control intervention for Plasmodium knowlesi

Intervention	Total cost (MYR, 2025 prices)	Baseline case occurrence (2020/2021)	Reported case (2023)	Cases averted/Locality	Incremental cost (MYR)	ICER (MYR per case averted)
No Intervention	3912.92	–	–	0	–	–
ORS	30,507.17	15	2	13	26,594.25	2045.71
LLIN	18,089.35	5	0	5	14,176.43	2835.29
ORS + LLIN	39,764.14	7	1	6	35,851.22	5975.20

ORS, Outdoor Residual Spraying; LLIN, Long-Lasting Insecticidal Net; ITN, Insecticide-Treated Net; ICER, Incremental Cost-Effectiveness Ratio. ICERs calculated as (Incremental Cost)/(Incremental Effect) compared to the "No Intervention" baseline. Cases averted were estimated from the difference between baseline incidence (2020–2021) and cases reported during the intervention period (2023). Exchange rate: 1 MYR = 0.23 USD (World Bank, 2025). Approximate USD equivalents: ORS ICER = USD 470 per case averted; LLIN ICER = USD 652 per case averted; ORS + LLIN ICER = USD 1,374 per case averted

Under observed programme conditions, ORS was associated with the highest number of cases averted (n = 13) during the study period, while also achieving the lowest cost per case averted (MYR 2,045.71; approximately USD 470). The LLIN/ITN programme was associated with fewer cases averted (n = 5), with a higher cost per case averted (MYR 2,835.29; approximately USD 650).

The combined ORS + LLIN/ITN strategy was associated with a slightly higher number of cases averted than LLIN alone (n = 6) but incurred the highest cost per case averted (MYR 5,975.20; approximately USD 1375). These findings suggest that ORS demonstrated a more favourable cost-effectiveness profile within the study context, while combined strategies provided additional protection at substantially higher cost.

Sensitivity analysis

Table 4 summarises the results of the one-way sensitivity analysis for total annual costs across the three scenarios: best-case, base-case, and worst-case. Total costs increased from best- to worst-case scenario for all interventions. The no-intervention baseline consistently remained the least costly, while the combined ORS + LLIN/ITN programme was the most expensive under all scenarios. Among the single-programme interventions, ORS consistently had higher costs than LLIN/ITN. Despite variations in absolute costs, the relative ranking of programme costs remained unchanged, indicating that the cost estimates and the comparative conclusions are robust to plausible changes in key cost parameters.

Table 4.

One-way sensitivity analysis of total annual costs by intervention (MYR)

Vector control program	Best-case	Base-case	Worst-case
No intervention	3726.99	3912.92	4097.61
LLIN/ITN	16,923.11	18,089.35	19,568.21
ORS	26,462.23	30,507.17	37,183.59
ORS + LLIN	37,215.38	39,764.14	47,073.72

ORS, Outdoor Residual Spraying; LLIN, Long-Lasting Insecticidal Net; ITN, Insecticide-Treated Net. Note: Costs are in MYR; Sensitivity analysis varied key cost and effectiveness parameters across three scenarios: Base-case (observed values), Best-case (lower costs, higher effectiveness), and Worst-case (higher costs, lower effectiveness). Exchange rate: 1 MYR = 0.23 USD (World Bank, 2025). Approximate USD equivalents (base-case): No intervention = USD 900; ORS = USD 7,017; LLIN = USD 4,161; ORS + LLIN = USD 9,146

Quantitative parameter ranges for cost variation were derived from the observed cost differences between best-case, base-case, and worst-case scenarios presented in Table 4. Across all interventions, cost parameters varied by approximately −13% to + 22% from base-case values. For effectiveness, best-case and worst-case scenarios were defined qualitatively based on observed programme outcomes, as detailed quantitative ranges could not be empirically derived from the available data.

Discussion

Evidence strength and policy implications

This study demonstrates that the strength and applicability of cost-effectiveness evidence for malaria interventions vary considerably across transmission settings, with importance implications for programme planning and policy. Among the evaluated vector control strategies in Sabah, Malaysian Borneo, ORS emerged as the most favourable cost-effective intervention for controlling zoonotic P. knowlesi, with an ICER of MYR 2,046 (approximately USD 470) per case averted. This finding remained robust across all one-way sensitivity analyses, underscoring the consistency of ORS as an economically efficient intervention in this context.

These findings contribute to the broader economic evidence base supporting insecticide-based vector control interventions [26–29]. Most existing cost-effectiveness analyses underpinning WHO guidelines originate from Sub-Saharan Africa and focus on tools such as ITNs and IRS, which are optimized for interrupting indoor transmission of human malaria [30–32]. Syntheses of this literature suggest that integrated LLIN and IRS strategies often achieved the greatest impact in areas with intense transmission and insecticide resistance and have been widely reported as effective vector control strategies in such settings [33–39].

However, the relevance of this evidence to zoonotic malaria settings is limited. The present study addresses a fundamentally different transmission ecology in Southeast Asia, where outdoor-biting and outdoor-resting vectors substantially reduce the effectiveness of conventional indoor-focused interventions. This highlights the importance of context-specific economic evaluations to guide locally appropriate intervention portfolios, particularly in settings where zoonotic malaria predominates [2, 3, 40, 41].

The economic evaluation presented here provides a realistic, evidence-based costing framework to support resource allocation decisions by Malaysia’s Ministry of Health (MOH) across ORS, LLIN/ITN, and combined intervention strategies [2, 23, 38, 39].

Compared with global benchmarks reported by Conteh et al. (2021), the ICER for ORS is higher than the global median (USD 5.85–121.50 per case averted), reflecting the operational complexity of controlling zoonotic malaria involving outdoor-biting Anopheles vectors and macaque reservoir [14, 15].

However, these comparisons should be interpreted cautiously, as this study reports outcomes in cases averted rather than DALYs, limiting direct comparability with DALY-based cost-effectiveness thresholds [7, 13, 29]

Nevertheless, within a regionally context, ORS remains highly competitive, with cost-effectiveness comparable to Indonesia (USD 380–720 per DALY averted) and more favourable than estimates from Thailand (USD 650–850 per DALY averted) [42, 43].

From a health system perspective, an investment of MYR 100,000 in ORS could avert an estimated 49 zoonotic malaria cases, potentially yielding treatment cost savings of approximately MYR 166,600 (based on an average treatment cost of MYR 3400 per case), suggesting net cost savings under the assumptions applied in this analysis [9, 25].

At the household-level, ORS may also prevent catastrophic health expenditures, as an estimated 38% of malaria patients incur costs exceeding 25% of monthly household income. This corresponds to potential household savings of MYR 27,391–30,135 attributable to ORS intervention [9, 25].

Vector ecology and intervention targeting

In Sabah, the primary vector of P. knowlesi, Anopheles balabacensis, exhibits exophilic and exophagic behaviour, limiting the impact of indoor-based interventions. The ORS programme evaluated in this study was specifically designed to target these outdoor-biting vectors through the application of K-Othrine Polyzone, a polymer-enhanced deltamethrin formulation with prolonged residual activity of up to six months. This formulation adheres effectively to outdoor surfaces such as wood, concrete and vegetation, providing sustained control in peri-domestic environments [2, 37–45].

Importantly, K-Othrine Polyzone also retains residual efficacy on indoor surfaces, offering dual applicability in settings where zoonotic and human malaria vectors coexist. This flexibility allows the same formulation to be deployed for conventional IRS against endophilic vectors and ORS against exophilic vectors, without the need for separate insecticide stocks. Such operational simplification reduce procurement complexity, logistics costs, programme fragmentation, thereby enhancing overall efficiency and cost-effectiveness in resource-limited settings [2, 14, 46–49].

Cost-effectiveness and comparative analysis

The analysis demonstrates that ORS alone provides the most favourable cost-effectiveness profile under the observed programme conditions, averting the greatest number of cases at the lowest cost per case averted. LLIN/ITN alone prevented fewer cases, while the combined ORS + LLIN/ITN strategy, although marginally more effective than LLIN alone, incurred substantially higher costs per case averted (ICER MYR 5975; approximately USD 1,375). These findings reinforce the importance of aligning intervention selection with local epidemiology, vector behaviour, and cost considerations [9, 50, 51]

The lower cost-effectiveness of the combined ORS and LLIN/ITN strategy may reflect overlapping intervention effects and diminishing marginal returns when multiple interventions are applied simultaneously. While ORS primarily targets outdoor transmission and LLIN/ITN addresses indoor exposure, the incremental benefit of combining both strategies may be limited in settings where outdoor transmission predominates [1, 5, 13].

However, combined interventions may still offer advantages in terms of equity and coverage. Populations with mixed exposure patterns, such as agricultural and forest-related workers, may benefit from layered protection strategies. In such contexts, the combined approach may enhance coverage across diverse risk groups, even if it is less economically efficient overall [31, 33, 53, 54].

While ORS demonstrates a favourable cost-effectiveness profile in this study, these comparisons should be interpreted cautiously, as outcomes are expressed in cases averted rather than DALYs, limiting direct comparability with WHO-CHOICE cost-effectiveness thresholds. Accordingly, the findings are best interpreted within a programme-level, case-based economic framework [17–19, 22, 29, 33, 38].

Within the broader malaria interventions landscape, ORS occupies an intermediate position, demonstrating strong local cost-effectiveness while requiring further validation across different ecological and transmission contexts. This stratification of evidence can assist policymakers in distinguishing between core investments (e.g., ORS in Sabah) suitable for broad deployment and strategies warranting targeted or phased implementation.

Strategic resource allocation and future directions

These findings support a stratified, evidence-based deployment of vector control interventions is crucial to maximize public health impact and economic efficiency in zoonotic malaria settings. While combined LLIN–IRS strategies are often prioritized in high-transmission African contexts, the results from Sabah suggest that ORS alone demonstrated the most favourable cost-effectiveness profile under the observed programme of impact and efficiency for widespread implementation, making it suitable for both sporadic and high-burden areas (Mukim/Daerah Beban Tinggi) [1, 2, 9, 36–41].

Combined ORS and LLIN strategies may have a role as supplementary interventions for specific high-risk populations, such as agricultural, plantation or forest-frontier workers with frequent and unavoidable outdoor exposure. This targeted deployment mirrors selective approaches used for other malaria interventions, such as chemoprophylaxis for travellers or intermittent preventive treatment in pregnancy, rather than universal application. While ORS demonstrates a favourable cost-effectiveness profile within this study, classification using WHO-CHOICE thresholds should be interpreted cautiously due to differences in outcome measures [2, 9, 14, 33, 47].

Strengths and limitations

The principal strength of this study lies in its comprehensive, ingredient-based costing from the healthcare provider perspective, incorporating both capital and recurrent expenditures to generate realistic budget estimates. The evaluation of intervention scenarios aligned with national operational guidelines enhances the immediate policy relevance of the findings. Robustness was further supported through sensitivity analyses, which consistently identified ORS as the most favourable cost-effective strategy.

Several limitations should be considered. The one-year time horizon precludes assessment of long-term cost-effectiveness and sustainability. Effectiveness estimates were derived from routine programme data and may be influenced by temporal trends and external factors, including climate variability, changes in surveillance intensity, and health-seeking behaviour. The absence of consistent population denominator data limited the use of incidence rates, restricting comparison with studies reporting incidence-based outcomes. The cross-district comparison may also introduce potential selection bias due to differences in population characteristics and programme targeting across study sites.

While unit costs (cost per premises and cost per person) were calculated to improve interpretability, the absence of standardised population denominator data across all intervention localities precluded the calculation of incidence rates. Effectiveness is therefore reported as cases averted rather than incidence-based outcomes.

In addition, the analysis adopted a provider perspective, excluding patient-incurred and societal costs, which may underestimate the full economic benefits of malaria prevention. Finally, while the findings provides local evidence for Sabah, generalisability to other zoonotic malaria settings may be limited due to differences in vector species, human mobility and forest–interface dynamics.

Recommendations for program strengthening and future research

To strengthen malaria control in Malaysia and address remaining evidence gaps, several strategic directions are recommended:

1. Conduct longitudinal cost-effectiveness studies of ORS and combined strategies across diverse ecological zones in Sabah and Sarawak to inform sustainable, long-term financing. This is particularly important given that effectiveness estimates based on routine programme data may be influenced by unmeasured factors such as climate variability, improvements in surveillance systems, and changes in community behaviour. Effectiveness estimates were based on cases averted derived from routine programme data. However, this approach may limit comparability with studies reporting incidence rates or DALY-based outcomes. Future longitudinal designs would better account for these temporal and contextual variations, thereby strengthening the robustness and generalisability of cost-effectiveness evidence.

2. Strengthen entomological surveillance system for continuous monitoring of insecticide resistance in An. Balabacensis and other vectors to safeguard the efficacy of current formulations (e.g., K-Othrine Polyzone).

3. Invest in integrated digital tools, including mobile health platforms, GIS-enabled spatial data systems, and real-time dashboards for case reporting and vector surveillance, and foster multi-sectoral collaboration between health, forestry, wildlife, and environmental authorities to enhance operational efficiency, support spatial risk mapping and hotspot identification, and enable rapid, data-driven responses to zoonotic spillover events.

4. Undertake targeted operational research in areas with mixed malaria transmission to determine the optimal balance between Indoor Residual Spraying (IRS) and ORS, including the potential for indoor application of ORS to streamline logistics while maintaining high efficacy against exophilic vectors.

5. Future studies should incorporate probabilistic sensitivity analysis (e.g., Monte Carlo simulation) to better characterise parameter uncertainty and strengthen the robustness of economic estimates.

Conclusion

ORS demonstrates the most favourable cost-effectiveness profile under the observed programme conditions for P. knowlesi control in Sabah, with an incremental cost of MYR 2046 per case averted. Although combined ORS and LLIN strategies offer higher protective efficacy, their higher cost reduce economic efficiency under current programmatic constraints. A stratified allocation approach prioritising ORS in high-burden districts, maintaining LLINs where indoor exposure persists, and reserving combined strategies for the highest-risk populations offers a pragmatic and cost-conscious pathway toward sustained malaria control in Malaysia.

Abbreviations

ABC

Activity-Based Costing

DALY

Disability-adjusted life year

GDP

Gross domestic product

GTS

Global Technical Strategy

ICER

Incremental cost-effectiveness ratio

IRS

Indoor residual spraying

ITN

Insecticide-treated net

IVM

Integrated Vector Management

JKR

Jabatan Kerja Raya

JKN Sabah

Sabah State Health Department

LLIN

Long-Lasting Insecticidal Net

MOH

Ministry of Health

ORS

Outdoor Residual Spraying

PKD

District Health Office

MYR

Malaysian Ringgit

WHO

World Health Organization

WHO-CHOICE

World Health Organization choosing interventions that are cost-effective interventions

Author contributions

All authors contributed to the conceptualization, methodology, data curation, investigation, and formal analysis. All authors participated in writing—original draft preparation, review, and editing, and approved the final manuscript.

Funding

This work was supported by the Universiti Kebangsaan Malaysia Research University Grant (Geran Universiti Penyelidikan, GUP-2024-065) for data collection and publication of this article.

Data availability

The data that support the findings of this study are available from the Ministry of Health Malaysia. Restrictions apply to the availability of these data, which were used under license for the current study. Data are available from the authors upon reasonable request and with permission from the Ministry of Health Malaysia and the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia.

Declarations

Ethics approval and consent to participate

The study was approved by the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia (NMRR ID: NMRR-24-01534-YGN [IIR]) and the Universiti Kebangsaan Malaysia Research Ethics Committee (UKM JEP-2024-317). All procedures were conducted in accordance with the ethical standards of the institutional and national research committees.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.