Skip to main content

The impact of mass screening and treatment interventions on malaria incidence and prevalence: a retrospective analysis of a malaria elimination programme in eastern Myanmar, and systematic review and meta-analysis

Abstract

Background

Targeted interventions are often needed to accelerate malaria elimination efforts. Mass screening and treatment (MSAT) involves testing all eligible and consenting individuals in an area for malaria and treating all positive individuals simultaneously. However, there are concerns regarding the impact of MSAT. This study evaluates the impact of MSAT on malaria incidence in Karen State, Myanmar, using routine surveillance data, and investigates the impact of MSAT in other settings through a systematic review and meta-analysis.

Methods

To investigate the impact of MSAT in Karen State, we retrospectively analysed routine malaria surveillance data collected in 10 villages where MSAT was done in 2018. Pre- and post-MSAT malaria incidences were compared, and a negative binomial mixed-effects model was used to estimate the relative change in monthly incidence for each additional year since MSAT.

To investigate the impact of MSAT in other settings, we searched Scopus, Ovid MEDLINE, and Web of Science (end date 11th July 2022) for studies assessing the impact of MSAT interventions on the incidence or prevalence of malaria infections. Studies were summarized, and a random-effects meta-analysis was performed on studies grouped according to study design and the comparator used to assess the impact of MSAT.

Results

In the 10 villages in Karen State, there was an overall reduction in P. falciparum incidence following MSAT (Incidence Rate Ratio 0.37; 95% CI: 0.19, 0.73). However, this is likely due to the ongoing impact of early diagnosis and treatment services offered in these communities, as shown by an overall reduction in incidence in the surrounding area. Results from nine studies identified in the systematic review demonstrate the variable impact of MSAT, which is likely influenced by a variety of factors, including intervention coverage and uptake, baseline malaria endemicity, and methods used for MSAT delivery.

Conclusions

This retrospective analysis and systemic review highlights the complexities behind the success of targeted interventions for malaria elimination. While these interventions are important drivers for achieving elimination goals, particularly in high-burden settings, it is important that various factors be considered when determining their suitability and how to optimize implementation.

Background

Early diagnosis and treatment of malaria cases is a cornerstone of elimination efforts. In some areas, continued early diagnosis and treatment uptake is sufficient to achieve local elimination. Still, in many regions, targeted interventions, including mass drug administration (MDA) and mass screening and treatment (MSAT), are required to overcome elimination barriers. These targeted malaria interventions aim to eliminate malaria cases in areas defined as “hotspots” based on high incidence or prevalence estimates or in areas where malaria transmission is low but residual transmission has prevented elimination [1].

During MDA, the entire eligible, consenting population is treated without diagnosis. This approach has proven effective in rapidly reducing Plasmodium falciparum incidence and prevalence in several studies across Southeast Asia and sub-Saharan Africa [1,2,3,4]. However, concerns that MDA could put selective pressure on parasites to develop artemisinin resistance have limited endorsement for its use despite evidence to suggest it does not [5,6,7,8]. As an alternative, during MSAT (also referred to as foci screening and treatment (FSAT)), the entire eligible, consenting population is screened, typically using rapid diagnostic tests (RDTs) or ultra-sensitive RDTs (uRDTs), and all positive cases are treated, reducing the number of treatments administered. However, the low sensitivity of these diagnostic tools means low parasite-density infections remain undetected [9, 10]. This limits the impact of MSAT on ongoing transmission, particularly in areas of low transmission where there is a higher proportion of subpatent infections which remain undetected and untreated [11].

In 2014, the Malaria Elimination Task Force (METF) programme deployed a network of malaria posts in villages across Karen State, Myanmar, which continue to provide access to early diagnosis and treatment [12]. In the period between 2014 and 2018, MDA was deployed by the METF programme in villages with a high prevalence of P. falciparum malaria detected in qPCR surveys (40% Plasmodium spp. prevalence overall and P. falciparum detected in 20% of Plasmodium-positive individuals). Despite the confirmed effectiveness of MDA interventions [2, 13], in 2018, the Myanmar National Malaria Control Programme (NMCP) ceased approval of MDA for P. falciparum malaria. As a result, from 2018 onwards, the METF programme replaced MDA with MSAT.

To date, three systematic reviews have been published on the effectiveness of MSAT in reducing malaria transmission [14,15,16]. However, community-wide MSAT delivery was not included in the selection criteria in these reviews, while the objective of this review is to assess the effectiveness of MSAT interventions delivered at the village level within a defined population. This study has two primary aims: firstly, to summarize the use and impact of MSAT interventions conducted by the METF programme on village-level P. falciparum incidence in Karen State, Myanmar, and secondly, to investigate and compare the impact of MSAT in other settings through a systematic review and meta-analysis of relevant literature.

Methods

Study design

To evaluate the association between MSAT and P. falciparum incidence, this retrospective study used surveillance data collected from 10 METF malaria posts where MSAT was deployed. The results from this analysis were then combined in a meta-analysis with studies identified from a systematic review of village-level MSAT interventions. Accordingly, the methods and results of this study are separated into two parts: (1) the analysis of MSAT in the METF programme and (2) the systematic review and meta-analysis of published MSAT studies.

MSAT in the METF programme

In 2018, the METF program conducted one round of MSAT in 10 villages (Fig. 1) in response to persistently high P. falciparum incidence (determined on a case-by-case basis) detected in weekly data collected by the malaria posts. MDA was conducted in two of the 10 villages approximately three years prior to MSAT.

Fig. 1
figure 1

Malaria posts that received an MSAT intervention. Malaria posts are coloured according to whether they did (black) or did not (grey) receive an MSAT intervention delivered by the METF programme

During MSAT, all consenting village residents were tested using uRDTs (NxTek™ Eliminate Malaria Pf, manufactured by Abbott Diagnostics Korea Inc.) and standard Plasmodium falciparumPlasmodium vivax RDTs (BiolineMalaria Ag P.f/P.v, Abbott Diagnostics Korea Inc). All consenting residents of the villages were eligible for inclusion except children younger than 6 months, individuals with an allergy to anti-malarial drugs, individuals who had received treatment for P. falciparum in the previous 7 days, and women in their first trimester of pregnancy. Individuals positive for P. falciparum by uRDT were treated with one round of dihydroartemisinin-piperaquine (7 mg/kg dihydroartemisinin, 55 mg/kg piperaquine) administered once per day for three consecutive days plus a single dose of primaquine (0.25 mg/kg). Pregnant women in their second or third trimester of pregnancy and breastfeeding women were eligible to receive dihydroartemisinin-piperaquine but not primaquine. Individuals positive for P. vivax by uRDT were treated with chloroquine once daily for three consecutive days (10 mg/kg on days 1 and 2, 5 mg/kg on day 3). The dormant liver stage of P. vivax parasites should typically be eliminated by treatment with an 8-aminoquinoline drug (radical cure), but this can result in haemolysis in glucose-6-phosphate-dehygrogenase (G6PD) deficient individuals [17,18,19]. Due to the presence of G6PD deficiency in the Karen population [17] and the absence of reliable G6PD testing during MSAT interventions, radical cure was not administered in this study.

Prior to MSAT, community engagement meetings were organized with the village leader and villagers to discuss the purpose of MSAT and how screening and treatment would be delivered. Larger settlements, typically consisting of military camps, logging camps, or mining sites near the target village, were also approached for inclusion in the MSAT intervention.

Statistical methods

For each month from when MSAT was conducted, P. falciparum and P. vivax incidence were calculated from weekly surveillance data as the number of cases over person-time exposed at the malaria post for the entire period of malaria post functioning. Person-time exposed was calculated at the malaria post level using village census data collected at the time of MSAT.

To estimate the relative change in P. falciparum and P. vivax monthly incidence for each additional year since MSAT, negative binomial mixed-effects modelling was performed with the population at each malaria post per month as the person-time denominator. Separate models were fit for P. falciparum and P. vivax to allow for differing impacts of MSAT on the incidence of the two malaria species. A random intercept was included for malaria posts to account for baseline village-level differences in incidence not accounted for in the models, a random slope was included for the number of years since MSAT, as well as its quadratic term to account for both linear and non-linear changes in temporal patterns between malaria posts. Fourier terms were included in the regression model to account for seasonality in malaria transmission over time. Some important confounders, including malaria post functionality, could not be accounted for in the model. Measures of malaria post functionality were collected during monitoring and evaluation assessments conducted at different points in time. Therefore, these indicators of functionality may not reflect the functionality of malaria posts over time. Additionally, the malaria posts opened at different time points, so they contributed variable amounts of data to the before- and after-MSAT periods. This could not be accounted for easily due to the dynamics between the date of malaria post opening, the date of MSAT delivery, and the date of malaria post closure. Statistical analyses were performed using R (version 3.6), and mapping was performed in ArcGIS Pro (version 2.5).

Systematic review

Search strategy and selection criteria

To be eligible for inclusion, studies needed to describe the implementation of MSAT at the village level in a malaria-endemic area, with the screening of individuals irrespective of symptoms. To assess the impact of MSAT, studies needed to present data either collected before and after the intervention or collected in intervention and control villages.

One reviewer performed database searches using Scopus, Ovid Medline, and Web of Science using the search strategy shown in Additional File 1, Box 1. Search results were uploaded to the Covidence platform [20], where duplicate articles were identified and removed by the platform’s automated methods. One reviewer screened the titles and abstracts of all unique records, and two reviewers screened the full texts of potentially relevant studies against the inclusion criteria. Studies that were deemed ineligible were recorded alongside the reasons for exclusion. Discussions between the two reviewers were used to resolve disagreements in study inclusions with the involvement of a third reviewer when necessary. This systematic review has been registered with PROSPERO under the registration number CRD42021279109.

Data extraction

Using an Excel template developed by two reviewers, one reviewer extracted information from the studies included in the systematic review, including country, malaria endemicity, study design, comparison intervention, the number of MSAT rounds conducted, population studied, diagnosis method, treatment provided to positive cases, and the outcome measure and effect measure.

Synthesis of results

Studies were summarized according to the study design, and the comparator used to assess the impact of MSAT. A random-effects meta-analysis was performed in R using the metafor package [21], with studies grouped according to study design and comparator used. The between-study heterogeneity was examined using Cochrane’s Q test and quantified with the (I2) value, which measures the percentage of the total variation in results across studies due to heterogeneity. The effect measure obtained from the analysis of METF data was included in the meta-analysis as the Incidence Rate Ratio (IRR) comparing incidence in the year prior to MSAT with the incidence in the two years post-MSAT.

Bias assessment

Two reviewers assessed the risk of bias for the included studies using the ROBINS-I tool [22] for non-randomized studies and the ROB2 tool [23] for randomized studies. Discussions between the two reviewers resolved disagreements in the bias assessment, with the involvement of a third author when necessary.

Results

MSAT in the METF programme

In 2018, MSAT was delivered in 10 villages, during which 1,248 individuals were tested using uRDTs. This corresponds to 94.1% (1248/1326) of the population screened according to census information collected prior to MSAT. Of the individuals tested, 12 P. falciparum cases were diagnosed and treated, corresponding to an overall test positivity of 0.96% (village-level positivity ranged from 0 to 3.4%) and a median (25 th–75 th percentile) village-level P. falciparum test positivity of 0.67% (0.1–1.5%). Standard RDTs detected no P. falciparum cases detected by uRDTs (0/12). MSAT was conducted on different dates across the 10 villages in 2018. However, all malaria posts had at least 34 months of pre-MSAT and 36 months of post-MSAT incidence data.

The monthly incidences of P. falciparum and P. vivax were also lower in the years preceding MSAT when compared to the year MSAT was delivered (Table 1). This reflects the unpredictable nature of the increase in incidence, which was the trigger for MSAT delivery. The monthly incidence of P. falciparum decreased by 63% (95% CI: 81–27% decrease) in the year after MSAT. This was in line with an overall decrease in P. falciparum incidence across the METF malaria post network of malaria posts over the same period, coinciding with the end of 2018 to 2021 (see Additional File 2, Figure S1). In the year following MSAT delivery, there was also a 40% decrease (95% CI: 55–20% decrease) in P. vivax monthly incidence in the year after MSAT when compared with the year prior to MSAT, despite P. vivax malaria cases not receiving radical cure during this period (Table 1).

Table 1 Relative change in monthly P. falciparum and P. vivax incidence by years since MSAT

An increase in P. falciparum incidence at the six-month time point after MSAT was representative of an increase in seven (70%) malaria posts, where this period coincided with the wet season transmission peak in 2019 (Fig. 2). The increase in P. falciparum and P. vivax incidence after the third year post-MSAT coincides with an increase in malaria transmission in seven malaria posts following the military coup in Myanmar in February 2021 (Fig. 2), which resulted in changes in population movement fluctuations in Karen State. The mean monthly P. falciparum incidence for each malaria post that received MSAT separately is shown in Additional File 2, Fig. S2.

Fig. 2
figure 2

Mean monthly incidences of P. falciparum and P. vivax by months since MSAT intervention. The mean monthly incidence of P. falciparum (green line) and P. vivax (orange line) with corresponding 95% confidence intervals calculated for the METF malaria posts where mass screening and treatment (MSAT) was delivered according to the number of months since MSAT. The total number of malaria posts providing malaria services and providing weekly data is shown in grey. Data are centred around the date of MSAT, as indicated by the vertical line

Systematic review and meta-analysis

Description of studies

After screening the titles and abstracts of 549 articles published up until the 11 th of July 2022, the full texts of 30 potentially relevant studies were reviewed, of which nine were included in the systematic review (Fig. 3) and are summarized in Table 2. The studies included in this review were conducted across seven countries (six African countries and Indonesia) of varying malaria endemicity. The combined results of these studies are representative of more than 120 rounds of MSAT, with a median of 3 (range: 1–85) MSAT rounds conducted in each study. In the studies which reported the results of screening (all except Larsen et al. [24]), 240,810 individuals were tested, resulting in the diagnosis of 74,756 P. falciparum cases, which corresponds to an overall positivity rate of 31% and a mean (range) positivity rate per study of 9.9% (0.2–41.5%).

Fig. 3
figure 3

Flow diagram of village-based mass screening and treatment (MSAT) studies identified during screening. *Studies were excluded if data were already presented in an included study which was published at an earlier date

Table 2 Summary of studies included in the systematic review

Four studies were randomized controlled trials [24,25,26,27], three were non-randomized controlled trials [28,29,30], and two were longitudinal cohorts [31, 32]. Of the four randomized controlled trials, three randomly selected communities or community clusters to receive MSAT or the standard of care [24, 25, 27], whereas in the study by Desai et al. intervention and control clusters were purposively selected based on criteria including malaria burden and access to road networks for the transport of samples in the study [26, 33]. In the three non-randomized controlled trials, high- and low-incidence clusters were included in both intervention and control arms [28, 29], or MSAT was delivered in high-incidence clusters only [30].

Limited information was provided on the age and sex of the participants included in MSAT rounds; however, in the five studies that did report the sex distribution of participants, approximately 50% were male [25,26,27,28, 31]. In the study by Sutcliffe et al., the majority of individuals screened were less than 15 years of age [25]. In the studies by Mlacha et al. and Desai et al. [26, 28] (only study 4.2 in Table 2), approximately 50 and 40% were less than 15 years of age, respectively, while in the study by Searle et al. [31], the maximum age of surveyed individuals was 33 years of age. No details were provided on the number of individuals within each age bracket in the study by Searle et al. Since the included studies did not provide census information, it was not possible to determine whether the age and sex distributions of the study population were representative of the actual population.

In seven of the nine studies, multiple rounds of MSAT were conducted either during consecutive months [24, 26, 27, 29], within a defined time period [24, 25, 32], or in response to the identification of P. falciparum cases during passive case detection [28, 31]. In the majority of studies (67%, 6/9), MSAT was conducted during household visits [24,25,26, 29,30,31]. However, this did not result in higher coverage rates compared with studies that conducted MSAT at a location within the village where everyone was screened [27, 28, 32] (Table 2).

The impact of MSAT was assessed either by comparing post-MSAT P. falciparum incidence in intervention and control villages [24, 26, 30], by comparing post-MSAT P. falciparum prevalence estimates collected during cross-sectional surveys in intervention and control villages [25, 28], or by comparing P. falciparum prevalence before and after MSAT using cross-sectional surveys [27, 29, 31, 32]. In four of the nine studies, multiple measurements of MSAT impact were presented, resulting in a total of 14 effect measurements recorded across the included studies (Table 2). In the studies by Sutanto et al. and Sutcliffe et al., a different number of MSAT rounds were conducted in two population cohorts [25, 27]; in the study by Desai et al., the impact of MSAT was assessed either through passive case detection or active case detection [26]; and in the study by Searle et al., the impact of MSAT on P. falciparum prevalence at varying distances from index households was investigated [31].

Across the nine studies, the impact of MSAT was measured after differing time intervals. In the study by Sutcliffe et al., P. falciparum prevalence was measured only once (before MSAT) in households in the cross-sectional cohort which acted as the control and was measured multiple times in the longitudinal cohort at the time of MSAT delivery over a one (study 1.1) or two-year period (study 1.2) [25]. In the study by Mlacha et al., P. falciparum prevalence was measured in a random subset of the population using cross-sectional surveys before and two and a half years after MSAT. In studies by Desai et al. and Larsen et al., passive case detection was conducted over a one-to-two-year period following intervention delivery in intervention and control villages through the network of local health facilities. In studies which compared P. falciparum prevalence before and after MSAT delivery, the follow-up period was between 30 and 90 days for all studies [27, 29, 31] except for the study by Bahk et al., which assessed the impact of MSAT in a follow-up survey two years after MSAT [32].

In several studies, multiple outcome measures were collected; however, relevant data were only provided for some. In the study by Sutanto et al., follow-up data was not presented for the control clusters where village-level screening was not conducted [27]. Accordingly, the prevalence estimate from the pre-MSAT period was used as the comparator for the Sutanto et al. study in this review. In Cook et al., passive case detection and cross-sectional surveys were used to assess the impact of MSAT; however, P. falciparum incidence measurements were not provided in the results of this study (incidence only shown graphically) [29]. For the study by Larsen et al., the impact of MSAT was assessed using cross-sectional surveys and passive case detection, but results were presented for passive case detection only (authors only provide the percent change in prevalence before and after MSAT from survey data) [24].

In eight of the nine studies, insecticide-treated nets were distributed either before programme commencement [24,25,26], as part of the study [27, 28], or by a different organization during the study [29,30,31]. The dominant vector species was mentioned in seven of the nine studies and included Anopheles gambiae [26,27,28], Anopheles funestus [25, 26, 30, 32], Anopheles arabiensis [24, 25, 30, 31], and Anopheles barbirostris [27].

MSAT study results and meta-analysis

To compare the impact of MSAT interventions across the studies included in this review, a meta-analysis was performed on studies grouped according to the comparator and the effect measure used in the assessment of MSAT. To allow for the comparison of METF results with results from the other studies using the pre-intervention period as the comparator, METF results were included in the meta-analysis as the incidence rate ratio comparing the incidence in the year prior to MSAT with the incidence in the two years post-MSAT. The meta-analysis included all studies except for the study by Conner et al., in which MSAT was conducted alongside other interventions so the effect measure (IRR = 0.62, 95% CI: 0.45, 0.84) cannot be used to assess the impact of MSAT alone [30], and the study by Desai et al. (study 4.2) in which active screening was performed on a random subset of the same population analysed during passive case detection in study 4.1 [26]. All other studies with two or more intervention arms assessed the impact of MSAT in separate sub-groups of the target population [25, 27, 31]. Slight differences between the confidence intervals reported in Sutcliffe et al. and those reported in Fig. 4 are a result of rounding errors.

Fig. 4
figure 4

Impact of MSAT interventions on P. falciparum incidence and prevalence. Random-effects (RE) meta-analysis model for studies grouped according to the comparator and effect measure used to assess the impact of mass screening and treatment (MSAT) on P. falciparum incidence, using incidence rate ratio (IRR), or P. falciparum prevalence, using the odds ratio (OR) or prevalence ratio (PR). Multiple estimates were included for studies which delivered or measured the impact of MSAT using multiple methods

In the two randomized controlled trials which assessed the impact of MSAT using cross-sectional surveys, the pooled Odds Ratio (OR) shows a reduction in the odds of P. falciparum positivity in villages that received MSAT when compared with control villages (OR = 0.30, 95% CI: 0.20, 0.45, I2 = 24.3%) [25, 28] (Fig. 4). In the study by Sutcliffe et al., there was a greater reduction in the odds of P. falciparum positivity following MSAT in the 2008/2009 cohort (OR = 0.12, 95% CI: 0.04, 0.37) when compared with the 2007 cohort (OR = 0.32, 95% CI: 0.13, 0.79) where the baseline prevalence of P. falciparum, measured at the first study visit prior to MSAT delivery, was higher for the 2007 cohort (Table 2).

In the two cluster randomized controlled trials which assessed the impact of MSAT through passive case detection, the pooled IRR shows a reduction in P. falciparum incidence in the villages that received MSAT when compared with control villages one-to-two-year post-MSAT (IRR = 0.81, 95% CI: 0.70, 0.95, I2 = 0.0%) (Fig. 4) [24, 26]. In study 4.2 by Desai et al. (excluded from the meta-analysis), there was a decline in P. falciparum incidence following MSAT during cross-sectional surveys in a random subset of the population included in study 4.1 (IRR = 0.95, 95% CI: 0.87, 1.04) [26].

The pooled Prevalence Ratio (PR) from studies which compared the post-MSAT P. falciparum prevalence to the pre-MSAT prevalence was 0.54 (95% CI: 0.34, 0.87, I2 = 72.7%). In studies by Bahk et al., Searle et al., and Sutanto et al., the effect measure was derived from the prevalence estimates provided in each of the studies for this review, so it does not account for other covariates including season and demographic factors, which may be important to consider in these studies [27, 31, 32].

In the METF analysis and studies by Mlacha et al. and Searle et al., MSAT was deployed in villages or households in response to the diagnosis of P. falciparum cases at health facilities [28, 31]. These interventions resulted in a decrease in P. falciparum incidence in the METF area (IRR = 0.16, 95% CI: 0.06, 0.40), a reduction in P. falciparum prevalence in the study by Mlacha et al. (OR = 0.34, 95% CI: 0.26, 0.44) [28], and a decrease in P. falciparum prevalence in the study by Searle et al. (PR = 0.36, 95% CI: 0.14, 0.90) at the households of index cases, but not at the households within a 250 m radius of the index households (Table 2) [31].

Comparisons between studies with different P. falciparum positivity rates and proportions of the population screened during each round of MSAT did not reveal any clear relationships between these factors and the resulting impact of MSAT (Table 2 and Fig. 4).

Risk of bias assessment

All studies included in the meta-analysis (Fig. 4) underwent a risk of bias assessment, with studies grouped according to whether the delivery of MSAT was randomized (see Additional File 3, Table S2 and S3). In the non-randomized trials, there were concerns about the selection of participants in two studies, Bahk et al. and the METF study, because MSAT was delivered at several time points, resulting in variable amounts of follow-up time, which were not accounted for in the analyses [32]. The risk of confounding in non-randomized trials was assessed as low based on the fact that confounding was explicitly addressed in these studies [22]. However, residual confounding, particularly due to unmeasured time-varying confounding and the small number of clusters included in some studies, remains a possibility. In the studies by Mlacha et al. and Bahk et al., the impact of MSAT was assessed in a random subset of between 31 and 56% of the population (different coverage between MSAT rounds), meaning the outcome measure was missing for much of the target population [28, 32].

In two of the four randomized controlled trials [24, 25], individuals were recruited following the randomization of clusters to intervention and control arms. In the study by Sutcliffe et al., this is unlikely to have had an impact on the recruitment of individuals into the study because MSAT was delivered at least once in both study arms [25], whereas in the study by Larsen et al., it is less clear whether this would have affected recruitment [24], so there are some concerns around the recruitment process in this study. Additionally, in the study by Sutcliffe et al., there were differences in insecticide-treated net ownership and usage and treatment-seeking behaviour between the intervention and control arms [25], and in the study by Larsen et al., there were differences in insecticide-treated net ownership and indoor residual spraying in the previous 12 months between the intervention and control arms [24]. These differences could indicate issues in the randomization process and may have influenced the impact of MSAT in these studies. More information on the distribution of households and the randomization process would help alleviate doubts about the randomization process in these studies.

Discussion

This study presents a retrospective analysis of 10 single-round MSAT interventions conducted at the village level by the METF programme in Eastern Myanmar alongside a systematic review and meta-analysis of nine studies of village-level MSAT interventions. In the METF programme, an overall reduction in P. falciparum incidence was seen in the 10 villages that received MSAT. However, the continued availability and uptake of early diagnosis and treatment services provided by the METF malaria posts is likely the major contributing factor in the decline of P. falciparum incidence at the villages which received MSAT, as region-wide declines in P. falciparum incidence were observed over the period in which MSAT was administered and assessed. A limitation of the METF analysis is that no control group was selected during MSAT to act as the comparator.

While all studies included in the meta-analysis (METF study results and eight studies identified during the systematic review) reported a reduction in the incidence or prevalence of P. falciparum following MSAT, the magnitude of the impact differed greatly and was likely influenced by a variety of factors including the coverage of MSAT in the target population, the baseline P. falciparum endemicity, and the methods used in MSAT delivery and assessment. This highlights the variable impact of MSAT in different settings.

The proportion of P. falciparum cases diagnosed and treated during MSAT rounds is a key factor in the impact of this intervention—the greater the proportion of P. falciparum cases detected and treated, the greater the reduction in the reservoir of infections remaining in the community. While MSAT and active screening interventions, such as the “1–3–7” approach, have been suggested for low transmission areas, low positivity rates and the limited diagnostic sensitivity of RDTs and uRDTs inherently limit the impact of these strategies [34, 35]. This was also identified as a limitation in several studies included in this review [24, 26, 32]. It is, therefore, essential that a large proportion of the target population is screened to detect as many P. falciparum cases as possible during MSAT. In the METF programme, while the overall detection of malaria infections was low, using uRDTs during MSAT increased the number of P. falciparum cases detected compared to standard RDTs. However, the ability of uRDTs and RDTs to detect the majority of cases depends on the proportion of low-density parasite infections in the community [35].

In several studies, only 50% of the target population was screened in one or more MSAT rounds [28, 29, 31, 32]. The reasons for low MSAT coverage provided by these studies were absenteeism at the time of screening [29, 31], insufficient community engagement before repeated screening rounds [29], or screening limited to a random subset of the population [28, 32]. While screening was done during household visits in the majority of studies [24,25,26, 29,30,31], this did not impact MSAT coverage when compared with studies in which individuals attended screening at a location within the village [27, 28, 32].

In the studies by Mlacha et al. and Searle et al., MSAT was delivered in response to identifying P. falciparum cases at health facilities in the target area [28, 31]. In these studies, there was a reduction in P. falciparum prevalence in the households of index cases following MSAT, but not in households within a 250 m radius of index households [31] where population coverage during screening was lower. Based on the studies included in this review, there is no clear relationship between the coverage of MSAT or positivity rate and the reduction in P. falciparum prevalence or incidence. While both factors play a role in MSAT impact, their importance likely depends on context-specific factors, including access to early diagnosis and treatment, the prevalence of asymptomatic infections, adherence to prescribed antimalarials, and demographic factors.

Demographic information, including the gender and age of individuals in the intervention, can provide insight into possible reasons for low intervention coverage. Of the studies that did provide demographic information, there was an almost equal distribution of females and males. However, the age distribution suggests limited coverage in older individuals [25, 27, 29, 30], which may indicate limitations in the delivery of MSAT in these studies.

In four studies, including the METF programme [27, 31, 32], P. falciparum incidence or prevalence measured after MSAT was compared to measurements collected prior to MSAT. In these studies, it is difficult to distinguish between the impact of MSAT and the decline in incidence over time, which would have occurred in the absence of MSAT. For example, in the METF programme, there was an overall decline in P. falciparum incidence in the METF programme area over the period coinciding with the post-MSAT period [12], which is likely the driver of the decline in MSAT villages as well.

One limitation of this review is that it was not possible to discern what impact individual factors had on the success of MSAT due to the wide range of methods used in MSAT delivery and differences in the study areas where MSAT was delivered. Another limitation is that due to differences in the comparator and outcome measures used, it was not possible to compare and pool the effect of MSAT across all studies. When used alone, prevalence and incidence measures of intervention impact both have limitations. Prevalence estimates provide only a snapshot of the malaria burden and, depending on malaria seasonality may overestimate or underestimate the impact of interventions. On the other hand, the treatment-seeking behaviour of the study population influences incidence measurements collected during passive case detection. To provide more reliable estimates of the impact of population-level malaria interventions, a combination of prevalence measured using repeated cross-sectional surveys and incidence measured through passive case detection should be used to compare intervention and control villages matched on a range of factors, including baseline malaria incidence or prevalence.

Conclusion

This retrospective analysis of MSAT interventions conducted by the METF programme, presented alongside a systematic review and meta-analysis of other studies evaluating the impact of village-based MSAT interventions, reveals the complexities behind the success of targeted interventions for malaria elimination. In the METF programme, the overall decline in P. falciparum incidence across the malaria post network was the likely driver of the decline in incidence following MSAT administration in the 10 villages that received MSAT. Across a variety of endemicities, the nine MSAT studies identified in the systemic review demonstrated a general reduction in P. falciparum incidence and prevalence following MSAT. The magnitude of this impact differed between studies, likely influenced by a wide range of factors from baseline endemicity, population demographics, and the timing and uptake of the intervention.

Availability of data and materials

The data analysed for this study are available upon request to the Mahidol-Oxford Tropical Medicine Research Unit data access committee: https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing.

References

  1. Eisele TP, Bennett A, Silumbe K, Finn TP, Chalwe V, Kamuliwo M, et al. Short-term impact of mass drug administration with dihydroartemisinin plus piperaquine on malaria in Southern Province Zambia: a cluster-randomized controlled trial. J Infect Dis. 2016;214:1831–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. von Seidlein L, Peto TJ, Landier J, Nguyen TN, Tripura R, Phommasone K, et al. The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: a cluster randomised trial. PLoS Med. 2019;16: e1002745.

    Article  Google Scholar 

  3. McLean ARD, Indrasuta C, Khant ZS, Phyo AK, Maung SM, Heaton J, et al. Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial. Lancet Infect Dis. 2021;21:1579–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Song J, Socheat D, Tan B, Dara P, Deng C, Sokunthea S, et al. Rapid and effective malaria control in Cambodia through mass administration of artemisinin-piperaquine. Malar J. 2010;9:57.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kaehler N, Adhikari B, Cheah PY, Day NPJ, Paris DH, Tanner M, et al. The promise, problems and pitfalls of mass drug administration for malaria elimination: a qualitative study with scientists and policymakers. Int Health. 2019;11:166–76.

    Article  PubMed  Google Scholar 

  6. Eisele TP. Mass drug administration can be a valuable addition to the malaria elimination toolbox. Malar J. 2019;18:281.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Imwong M, Dhorda M, Myo Tun K, Thu AM, Phyo AP, Proux S, et al. Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong Subregion: an observational study. Lancet Infect Dis. 2020;20:1470–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Deng C, Wu W, Yuan Y, Li G, Zhang H, Zheng S, et al. Malaria control by mass drug administration with artemisinin plus piperaquine on Grande Comore Island, Union of Comoros. Open Forum Infect Dis. 2023;10:ofad076.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rogier E, Hamre KES, Joseph V, Plucinski MM, Presume J, Romilus I, et al. Conventional and high-sensitivity malaria rapid diagnostic test performance in 2 transmission settings: Haiti 2017. J Infect Dis. 2020;221:786–95.

    CAS  PubMed  Google Scholar 

  10. Yeung S, McGregor D, James N, Kheang ST, Kim S, Khim N, et al. Performance of ultrasensitive rapid diagnostic tests for detecting asymptomatic Plasmodium falciparum. Am J Trop Med Hyg. 2020;102:307–9.

    Article  PubMed  Google Scholar 

  11. Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3:1237.

    Article  PubMed  Google Scholar 

  12. Rae JD, Nosten S, Kajeechiwa L, Wiladphaingern J, Parker DM, Landier J, et al. Surveillance to achieve malaria elimination in Eastern Myanmar: a 7-year observational study. Malar J. 2022;21:175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Landier J, Parker DM, Thu AM, Lwin KM, Delmas G, Nosten FH, et al. Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on P. falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme. Lancet. 2018;391:1916–26.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bhamani B, Mithi V, Whitfield K, Tusell M, Coma-Cros EM, Serra E, et al. Mass test and treat as an accelerator strategy for malaria elimination: a systematic review. WHO Guidelines for Malaria. Geneva: World Health Organization; 2022.

    Google Scholar 

  15. Kim S, Luande VN, Rocklov J, Carlton JM, Tozan Y. A systematic review of the evidence on the effectiveness and cost-effectiveness of mass screen-and-treat interventions for malaria control. Am J Trop Med Hyg. 2021;105:1722–31.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Newby G, Cotter C, Roh ME, Harvard K, Bennett A, Hwang J, et al. Testing and treatment for malaria elimination: a systematic review. Malar J. 2023;22:254.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bancone G, Chu CS, Somsakchaicharoen R, Chowwiwat N, Parker DM, Charunwatthana P, et al. Characterization of G6PD genotypes and phenotypes on the Northwestern Thailand-Myanmar border. PLoS ONE. 2014;9: e116063.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Chu CS, Bancone G, Moore KA, Win HH, Thitipanawan N, Po C, et al. Haemolysis in G6PD heterozygous females treated with primaquine for Plasmodium vivax malaria: a nested cohort in a trial of radical curative regimens. PLoS Med. 2017;14: e1002224.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chu CS, Bancone G, Nosten F, White NJ, Luzzatto L. Primaquine-induced haemolysis in females heterozygous for G6PD deficiency. Malar J. 2018;17:101.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Covidence systematic review software. Melbourne, Australia: Veritas Health Innovation. www.covidence.org. Accessed 6 Feb 2025.

  21. Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.

    Article  Google Scholar 

  22. Risk of bias tools - Current version of ROBINS-I. https://www.riskofbias.info/welcome/home/current-version-of-robins-i.

  23. Risk of bias tools - Current version of RoB 2. https://www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2.

  24. Larsen DA, Bennett A, Silumbe K, Hamainza B, Yukich JO, Keating J, et al. Population-wide malaria testing and treatment with rapid diagnostic tests and artemether-lumefantrine in Southern Zambia: a community randomized step-wedge control trial design. Am J Trop Med Hyg. 2015;92:913–21.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sutcliffe CG, Kobayashi T, Hamapumbu H, Shields T, Mharakurwa S, Thuma PE, et al. Reduced risk of malaria parasitemia following household screening and treatment: a cross-sectional and longitudinal cohort study. PLoS ONE. 2012;7: e31396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Desai MR, Samuels AM, Odongo W, Williamson J, Odero NA, Otieno K, et al. Impact of intermittent mass testing and treatment on incidence of malaria infection in a high transmission area of Western Kenya. Am J Trop Med Hyg. 2020;103:369–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sutanto I, Kosasih A, Elyazar IRF, Simanjuntak DR, Larasati TA, Dahlan MS, et al. Negligible impact of mass screening and treatment on mesoendemic malaria transmission at West Timor in Eastern Indonesia: a cluster-randomized trial. Clin Infect Dis. 2018;67:1364–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mlacha YP, Wang D, Chaki PP, Gavana T, Zhou Z, Michael MG, et al. Effectiveness of the innovative 1,7-malaria reactive community-based testing and response (1, 7-mRCTR) approach on malaria burden reduction in Southeastern Tanzania. Malar J. 2020;19:292.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cook J, Xu W, Msellem M, Vonk M, Bergström B, Gosling R, et al. Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar. J Infect Dis. 2015;211:1476–83.

    Article  CAS  PubMed  Google Scholar 

  30. Conner RO, Dieye Y, Hainsworth M, Tall A, Cissé B, Faye F, et al. Mass testing and treatment for malaria followed by weekly fever screening, testing and treatment in Northern Senegal: feasibility, cost and impact. Malar J. 2020;19:252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Searle KM, Katowa B, Musonda M, Pringle JC, Hamapumbu H, Matoba J, et al. Sustained malaria transmission despite reactive screen-and-treat in a low-transmission area of Southern Zambia. Am J Trop Med Hyg. 2020;104:671–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Bahk YY, Cho PY, Ahn SK, Lee WJ, Kim TS, Uganda, et al. An evaluation of active case detection in malaria control program in Kiyuni Parish of Kyankwanzi District, Uganda. Korean J Parasitol. 2018;56:625–32.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Samuels AM, Awino N, Odongo W, Benard A, Gimnig J, Otieno K, et al. Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial. Malar J. 2017;16:240.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Mukaka M, Peerawaranun P, Parker DM, Kajeechiwa L, Nosten FH, Nguyen TN, et al. Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection. Malar J. 2021;20:351.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mwesigwa J, Slater H, Bradley J, Saidy B, Ceesay F, Whittaker C, et al. Field performance of the malaria highly sensitive rapid diagnostic test in a setting of varying malaria transmission. Malar J. 2019;18:288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the hard work of malaria post workers in the METF programme and all the communities in Karen state who are dedicated to achieving malaria elimination in the region.

Funding

Open access funding provided by Mahidol University. SMRU is part of Mahidol Oxford Research Unit supported by the Wellcome Trust of Great Britain. This research was funded in part by the Wellcome Trust (220211), The Bill & Melinda Gates Foundation (OPP1117507), and the Regional Artemisinin Initiative RAI and RAI2E (Global Fund against AIDS, Tuberculosis and Malaria). JAS was supported by an Australian National Health and Medical Research Council of Australia (NHMRC) Investigator Grant (1196068). RJM was supported by The Bill and Melinda Gates Foundation (OPP1193472). AD was supported by an Australian NHMRC Investigator Grant (2025362). The funders had no role in the design, conduct, or analysis of the study. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Author information

Authors and Affiliations

Authors

Contributions

JDR, AD, FHN, JAS and RJM contributed to the conceptualisation of the study. GD, LK, MMT, SWT and AMT provided essential support to the functioning of the programme. JDR, JW, CP and AMT contributed to the collection and processing of data from the METF programme. JDR, AD, CP, and AMT contributed to the conducting of the systematic review. JDR performed the formal analysis. JDR wrote the draft manuscript. JDR, AD, AMT, DMP, RJM, JAS, and FHN contributed to the writing, reviewing, and editing of the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jade D. Rae.

Ethics declarations

Ethics approval and consent to participate

The METF programme is approved through the Ethics Review Committee on Medical Research Involving Human Subjects from the Republic of the Union of Myanmar, Ministry of Health and Sports, Department of Medical Research (Lower Myanmar): 73/Ethics 2014.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Julie A. Simpson and François H. Nosten are joint last co-authors.

Supplementary Information

Additional file 1: Box 1. Search strategy for systematic review.

12936_2025_5392_MOESM2_ESM.pdf

Additional file 2: Fig. S1. Mean monthly incidence ofP. falciparum andP. vivax across all METF malaria posts. Fig. S2. Mean monthly incidence for P. falciparum by months since MSAT intervention at METF malaria posts.

12936_2025_5392_MOESM3_ESM.pdf

Additional file 3: Table S2. Risk of bias assessment performed using ROBINS-I for non-randomized trials. Table S3. Risk of bias assessment performed using ROB-2 for randomized trials.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rae, J.D., Devine, A., Patekkham, C. et al. The impact of mass screening and treatment interventions on malaria incidence and prevalence: a retrospective analysis of a malaria elimination programme in eastern Myanmar, and systematic review and meta-analysis. Malar J 24, 148 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12936-025-05392-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12936-025-05392-9