Eliminating Plasmodium Falciparum Malaria: Results From Tailoring Active Case Detection Approaches to Remote Populations in Forested Border Areas in North-eastern Cambodia

doi:10.21203/rs.3.rs-98597/v1

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Case study

Eliminating Plasmodium Falciparum Malaria: Results From Tailoring Active Case Detection Approaches to Remote Populations in Forested Border Areas in North-eastern Cambodia

https://doi.org/10.21203/rs.3.rs-98597/v1

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published 22 Feb, 2021

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Background: Remaining Plasmodium falciparum cases in Cambodia are concentrated in forested border areas and in remote populations who are hard to reach through passive case detection. A key approach to reach these populations is active case detection by mobile malaria workers (MMWs). However, this is operationally challenging because of changing movement patterns of the target population moving into less accessible areas. From 2018 to 2020, a tailored package of active case detection approaches was implemented in forested border areas of three provinces in north-eastern Cambodia to reach remote populations and support the elimination of P. falciparum malaria.

Approach: Key elements of this project were to tailor approaches to local populations, use responsive monitoring systems, maintain operational flexibility, build strong relationships with local communities, and implement close supervision practices. MMWs were recruited from local communities. Proactive case detection approaches included mobile malaria posts positioned at frequented locations around and within forests, and locally informed outreach activities targeting more remote locations. Reactive case detection was conducted among co-travellers of confirmed cases. Tests were conducted independent of fever symptoms. Routine monitoring informed tactical adaptations, while supervision exercises ensured service quality.

Results: Despite operational challenges, between January 2018 and June 2020, service delivery sites were able to maintain consistently high testing rates, with each site testing a monthly average of > 60 people in 2020. Over the project period, the P. falciparum/ P. vivax ratio has steadily inversed. In 2020, MMWs detected only 22 P. falciparum cases with constant testing rates. Including data from neighbouring health facilities and village malaria workers, 52% of all people tested and 40% of P. falciparum cases detected in the area can be attributed to MMWs.

Remaining challenges: Maintaining intensified elimination efforts, addressing the issue of detecting low parasitemia cases and shifting focus to P. vivax malaria challenge the last phase of malaria elimination.

Conclusions: Reaching remote populations through active case detection should remain a key strategy to eliminate P. falciparum malaria. We have presented a successful approach combining tailored proactive and reactive strategies that could be transferred to similar settings in other areas of the Greater Mekong Subregion.

Infectious Diseases

Malaria elimination

Forest malaria

Early diagnosis and treatment

Case detection

Community health worker

Plasmodium falciparum

Mobile and migrant populations

Mobile malaria worker

Greater Mekong Subregion

Regional Artemisinin Initiative

Background

Cambodia has made huge progress towards eliminating Plasmodium falciparum (P. falciparum) malaria in recent years and is well on track to achieve its goal of eliminating malaria by the end of 2025 (1, 2). This can be attributed to intensified efforts to accelerate the elimination of P. falciparum malaria in the Greater Mekong Subregion (GMS) under the two consecutive Regional Artemisinin-resistance Initiative (RAI) programs since 2016.

In Cambodia, the RAI program focuses on international borders and forest areas where remaining malaria parasite reservoirs are clustered (1, 3–5). In these areas, the population at highest risk of malaria infection are mobile and migrant populations and forest workers (6–9) who often spend several nights in the forest at a time or even stay there permanently (5, 10). These populations are hard to reach via the common community-based passive case detection system. This system requires people to actively seek care with village malaria workers (VMWs) while mobile and migrant populations or forest workers might not know about the system in the first place or be hesitant to use it (6, 11–13). Expanding access to early diagnosis and effective treatment (EDAT) is a key element of the National Strategic Plan to Eliminate Malaria (1). In 2009, the National Center for Parasitology, Entomology and Malaria Control (CNM) therefore introduced the community health worker role of mobile malaria workers (MMWs) to target these remote populations with active case detection approaches (12). In border areas, this is challenging due to highly heterogeneous micro-geographical epidemiology, unexplored forest areas, difficult to access terrain and changing movement and behavioural patterns of populations.

Since 2018, Malaria Consortium has been delivering a tailored package of active case detection approaches through MMWs in selected hard to reach border areas in north-eastern Cambodia as a component under the second RAI program (RAI2E). The approach was developed in alignment with the National Strategic Plan for Elimination of Malaria, in close collaboration with the CNM. The RAI2E grant will conclude by the end of 2020 and be followed by RAI3, the third 3-year-grant-cycle in the GMS. The conclusion of the second grant cycle is an appropriate occasion to look back on the achievements during the RAI2E implementation period, to investigate challenges faced along the way, and to discuss priorities for the final phase of malaria elimination.

Objectives

This case study aims 1) to outline the approach to deliver a tailored package of active case detection approaches with the aim of providing EDAT services to remote populations in border areas of three provinces in north-eastern Cambodia under the RAI2E program, and 2) to describe results achieved and discuss remaining challenges for the last elimination phase.

Approach

Project setting

The project started in 2018 and will continue until December 2020. It was implemented in border areas of the three Cambodian provinces Preah Vihear, Stung Treng and Ratanakiri along the Laos, Thailand and Vietnam borders. Border areas in these provinces are forested and difficult to access, especially during the rainy season between May and October. The existing network of eight to ten MMWs working in the area prior to 2018 was scaled up to 50 MMWs as part of the project. MMWs work under the CNM and are assigned to specific health facilities that oversee the activities of their assigned community health workers (MMWs and VMWs) and provide them with treatment supplies. The target population was everyone living and working within the catchment area of the project sites with a focus on reaching the high risk population of adult males over the age of 15 as defined by the Malaria Elimination Action Framework 2016-20 (9).

Project design

The goal of this project was to contribute to the RAI2E objective of accelerating P. falciparum malaria elimination and the national objective of eliminating malaria by 2025 (1). The overall approach was to implement a tailored package of active case detection approaches through a network of MMWs in order to reach remote populations and deliver EDAT services in line with national treatment guidelines (14). The logic model of the project assumes that the efficient delivery of the package of tailored active case detection approaches in combination with quality case management would lead to effective detection and treatment of P. falciparum cases among target populations, contributing to the accelerated elimination of P. falciparum malaria in project areas.

The technical design of the project built on learnings from the first RAI program 2016–2017 where implementing partners had already gained experience operating in the project area and from other research projects in the same region. These lessons can be summarized into five guiding principles that informed the design of the current project: The need to tailor case detection approaches to the local target population and context, using responsive monitoring systems, maintaining operational flexibility, building strong community relationships, and closely supervising the MMW network.

1. Tailoring service delivery to the local target population and context: Efficient active case detection approaches have to consider the whole spectrum of the target population. Remote populations consist of various subpopulations, including local and mobile forest-workers, construction workers, security personnel and border-crossers, who are each involved in different forest-related activities (13). Active case detection approaches targeting these populations have to be tailored to each subpopulation individually leveraging local knowledge on population behaviour, movements and work sites. Reactive approaches have to target individuals sharing the same exposure time and location as the index case, i.e. co-travellers rather than household members (15–17).

2. Using responsive monitoring systems: Responsive monitoring systems are a key component to efficiently target interventions. Hotspots and population movements change constantly (18, 19) which requires routinely adjusting and optimizing operational timing and locations of testing. This can only be achieved by systematic monitoring practices facilitating collaborative decisions between all relevant stakeholders based on quantitative evidence, operational experience and local insights.

3. Maintaining operational flexibility: In order to respond to the findings from the responsive monitoring system in a timely manner, the operational set-up must allow the flexible adaptation of project activities.

4. Building strong community relationships: Any approach to reach remote populations must involve strong and sustained relationships with these communities. A key factor in achieving this is the recruitment of MMWs directly from the target communities of forest-goers and mobile and migrant populations which is essential to establish them as trusted service providers based on existing relationships and expert knowledge about the local environment (1).

5. Facilitating close supervision systems: Closely supervising the MMW network is needed to ensure quality of service delivery and to sustain motivation among health workers. This includes routine supervision practices by national and project staff, as well as regular meetings for MMWs to share their experiences and knowledge. Operationally, this means it is necessary to factor extensive travel by project staff in difficult road conditions and proper deployment of staff to guarantee effective operations, particularly during the rainy season.

Translation into practice

All project activities were aligned with the current National Strategic Plan for Elimination of Malaria and the Malaria Elimination Action Framework and were developed and delivered in close collaboration with the CNM (1, 9).

As per CNM guidelines, MMWs were directly recruited from local target communities (i.e. forest-goers or mobile and migrant populations) in high risk (i.e. annual parasite index greater than 5 per 1,000 population based on data from the national malaria information system (MIS)) and remote areas (i.e. more than 5 kilometres or more than one hour walk from the nearest health centre) where no other VMWs or MMWs worked. MMWs were trained on service delivery and case management in collaboration with the CNM who also conducted regular supervision visits. They were paid $20 per month by the CNM, and an additional $5 per day for each workday through the RAI2E project.

The package of active case detection approaches consisted of a combination of proactive case detection delivered through mobile malaria posts and outreach activities, and occasional reactive case detection among co-travellers of index cases. MMWs were assigned to work either at a mobile malaria post or an outreach site (where needed, two MMWs were assigned to work at the same site) and to approach everyone who passed by their post or that they met during their outreaches. People were tested without prior screening for fever. Operational targets for mobile malaria posts were to test 20 people per week and for outreach sites to conduct two outreach activities per week. Targets were set based on experiences from the first RAI program and feasibility considerations based on the available budget. In general, mobile malaria posts operated seven days per week with standard operating hours between 7am and 7 pm with operational flexibility to adjust to local population movement patterns. Additionally, where feasible, MMWs were asked to conduct reactive case detection if a confirmed malaria case had spent time in the forest in the previous two weeks. This consisted of identifying and screening co-travellers who were willing to be tested independent of fever symptoms. Active door-to-door screening was conducted in Preah Vihear in 2020 to confirm no new P. falciparum cases. Active case detection and EDAT services were complemented by distributing long lasting insecticide-treated nets and hammock nets (LLINs/LLIHNs) as well as conducting health education among target communities.

Malaria tests were conducted with combo P. falciparum/ Plasmodium vivax (P.vivax) rapid diagnostic tests (RDTs) (SD BIOLINE Malaria Ag P.f/P.v, Standard Diagnostics) applied as per product guidelines (20). Positive cases were treated directly with artemisinin-based combination therapy (ACT) where feasible and referred to associated health centres in case of treatment stock-outs, severe cases or contraindications in line with national guidelines (14). First-line treatment was artesunate-mefloquine with pyronaridine-artesunate used during prolonged stock-out of first line treatment. Single low-dose primaquine was given for P. falciparum and mixed cases. Tests, treatment and LLINs/ LLIHNs were supplied by associated health centres.

Mobile malaria posts were tactically placed at border crossings, at forest entry points or market places close to locations where the national MIS had reported high caseloads of P. falciparum or mixed cases and where target populations frequently passed by on their way to and from the forest. Outreach activities targeted areas close to or within the forest not covered by mobile malaria posts or where communities could not easily access health services (such as remote forests and workplaces).

The project further employed nine community mobilization officers tactically placed at field sites to directly support MMWs, a field implementation manager placed at a coordination office and a technical specialist. The team was responsible for ensuring the quality and efficiency of project delivery through monthly assessments and supervision of service delivery by MMWs with standardized checklist, and responsive monitoring. Responsive monitoring was focused on service delivery efficiency and coverage, case clustering, population movements and availability of treatment and test supplies. As part of these activities quantitative evidence, operational experience, and local knowledge were regularly reviewed to recognize emerging needs early on, and reprogram in collaboration with the CNM, local authorities and other implementing partners.

Data collection and analysis

This case study focuses on the implementation period between January 2018 and June 2020. Data analysis was based on routine data on people tested, positive cases, stock and other service delivery data recorded by MMWs. Data was entered in Excel and MS Access databases by community mobilization officers monthly, and integrated and verified by the field implementation manager. MIS data from health facilities associated with project MMWs and data from VMWs associated with the same health facilities from January 2018 to June 2020 was provided by the CNM. Quantitative data were summarized descriptively using Microsoft® Power BI Desktop (21). Information on operational considerations and challenges were summarized based on project reports compiled by project staff. The term P. falciparum cases includes P. falciparum and mixed cases.

Results are summarized to outline the operational aspects of the project concerning the efficiency and quality of service delivery, the effectiveness of active case detection approaches in reaching the target population and detecting new P. falciparum cases and the contribution of the project to the accelerated elimination of P. falciparum malaria in the project area.

Delivery of tailored active case detection approaches

Operational set-up

At the start of the project in January 2018, the goal agreed among stakeholders was to recruit 32 MMWs and deploy them at service delivery sites in border areas of the provinces Preah Vihear, Ratanakiri and Stung Treng (Fig. 1: Service delivery sites by project year from January 2018 to June 2020). Due to delays in the official project start, services were delivered through 23 service delivery sites until June 2018. After the official project start, the number of service delivery sites was quickly scaled up to the intended 32 sites and further expanded to 45 service delivery sites operated by 50 MMWs by November 2018. This expansion of services was coordinated with local authorities and other implementing partners to avoid overlapping of service delivery. Initial location of service delivery sites was based on risk areas identified during the first RAI program. Over the project period, responsive monitoring facilitated tactical relocations. Table 1 depicts the monthly average of service delivery sites by project year and project province.

Table 1

Monthly average of service delivery sites from January 2018 to June 2020
Province	Project year	Monthly average number of service delivery sites
		Mobile Malaria Posts	Outreach sites
Preah Vihear	2018	2	6
	2019	2	6
	2020^a	2	7
Ratanakiri	2018	2	10
	2019	4	16
	2020^a	4	19
Stung Treng	2018	3	5
	2019	5	11
	2020^a	5	11
^a Until June

Efficiency of service delivery

Figure 2 describes the efficiency of service delivery by proactive case detection approaches through the monthly average of people tested per site (Fig. 2: Monthly average of people tested per service delivery site by proactive case detection approach from January 2018 to June 2020). While in the first project year 2018 a monthly average of only 37 people was tested per site, targeted optimization strategies increased the monthly average of people tested per site in the subsequent project years to 62 in 2019 and 61 in 2020. Across project years, mobile malaria posts tested a monthly average of approximately twice as many people per site as outreach sites due to their continuous operations throughout the month while outreaches were point-in-time activities only taking place twice a week. The overall daily average of people tested taking into account only operational days was 4 people for both mobile malaria posts and outreach sites, showing that mobile malaria posts and outreach sites were equally efficient in testing people.

Due to natural differences in population movements, the monthly average of people tested per service delivery site differed between provinces with a lower monthly average of people tested in Preah Vihear due to a natural decline in local forest-goer activities.

Strategies to increase the monthly average of people tested included tactically relocating service delivery sites in close collaboration with local authorities and allowing MMWs to flexibly adapt their daily operations to align with forest-goer movements. Where needed, mobile malaria posts operated both early in the morning and late in the evening with alternating shifts between two MMWs. In 2020, some mobile malaria posts that saw fewer people crossing, operated as a mobile malaria post in the morning and conducted outreach activities in the evening, thereby improving the reach of their services. One strategy to respond to population movement changes in a timely and responsive manner was the development of a ‘seasonality calendar’: Through a workshop held in December 2018, project teams worked with MMWs to develop a calendar detailing when mobile and migrant populations usually participated in activities that increased the risk of malaria infection, including the shifts of construction and work sites within forests based on seasonality. The calendar was regularly updated and used by project staff to ensure that service delivery points were positioned at the right place at the right time.

Quality of case management

Table 2 depicts the number of people tested, cases found and proportion of positive cases treated and referred by project year. The tailored package of active case detection approaches facilitated the testing of 65,827 people for malaria and the detection of 4,196 positive malaria cases.

Of all positive cases (all plasmodium species), 86% were treated with ACT as per national guideline while the remaining 14% were referred to the nearest health facility to receive appropriate treatment. In the second and third quarter of 2018, primary service delivery sites experienced stock-outs of first and second line treatment supplies: only 79% of positive cases received ACT treatment at site while 21% of positive cases were referred to nearby health centres in 2018. Referral costs could be covered by project savings, but success of referral was not followed up, so actual reception of treatment could not be confirmed. During this period, a project implemented by Médecins Sans Frontières in the neighbouring district Chey Saen provided treatment supplies to support the sustainment of service delivery for a few weeks. Once stock-outs were resolved, the proportion of positive cases treated directly as per national guideline improved from 79% in 2018 to 97% in 2020.

In the beginning of the project, the appropriate dosage of single low-dose primaquine for P. falciparum positive cases people weighing < 50 kg (7.5 mg) was not available. However, monitoring data showed that a large proportion of P. falciparum cases in the project area actually required this dosage: 27% of adult (≥ 15 years old) and 43% of all positive P. falciparum cases in 2018 weighed < 50 kg. After this issue was raised to the CNM and the appropriate dosage was supplied to project areas in 2019, the proportion of P. falciparum cases treated with primaquine as per national guidelines improved from 9% in 2018 to 91% in 2020.

Table 2

Details on number of tests, cases detected and proportion of positive cases treated or referred from January 2018 to June 2020
Project year	People tested n (column %)	Positive cases detected n (row %)		Received treatment %
		P. falciparum	P. vivax	ACT^b	Referred^c	Primaquine^d
2018	13,407 (20)	934 (42)	1,264 (58)	79%	21%	9%
2019	33,300 (51)	314 (19)	1,309 (81)	92%	8%	51%
2020^a	19,120 (29)	22 (6)	353 (94)	97%	3%	91%
Total	65,827 (100%)	1,270 (30)	2,926 (70)	86%	14%	20%
^a Until June 2020 ^b Proportion of all positive cases who were treated with first-line artemisinin-combination therapy (ACT) ^c Proportion of all positive cases who were referred for any reason ^d Proportion of P. falciparum cases treated with single low-dose primaquine

Detection of P. falciparum cases among target population

Reaching the target population

Figure 3 shows the gender and age composition of the population that was tested and positive P. falciparum cases (Fig. 3: Age and gender composition of all people tested and P. falciparum positives from January 2018 to June 2020). People tested through the tailored active case detection package were predominantly male (61%) and over 15 years old (71%). Specifically, males over 15 years made up 45% of the total population tested and 62% of P. falciparum cases, while females over 15 years made up 26% of all people tested and 13% of P. falciparum cases. 26% of P. falciparum cases were children under 15 years old.

Effectiveness of case detection approaches in detecting P. falciparum cases

Table 3 describes the number of people tested to find 1 P. falciparum case by case detection approach. The number of people tested to find 1 P. falciparum case is the ratio of the number of people tested to the number of P. falciparum cases detected in a specified period. It is an indicator for the ‘effectiveness of a case detection approach’ compared to other approaches in similar settings and periods.

Overall, mobile malaria posts tested an average of 38 people to find 1 P. falciparum case, while an average of 76 people were tested to find 1 P. falciparum case through outreach activities. The number of people tested to find 1 case increased notably by project year which was driven by the decrease in total number of P. falciparum cases detected in the project area from 2018 to 2020. In each individual project year, mobile malaria posts needed to test less people to find 1 P. falciparum case than outreach activities, indicating that mobile malaria posts were more effective in detecting new P. falciparum cases than outreach activities in the given local context.

An average of 27 co-travellers were tested to find 1 P. falciparum case and no P. falciparum cases were found through active door-to-door screening. However, it should be taken into account that these two case detection approaches were conducted at a much smaller scale than mobile malaria posts and outreaches, hence limiting the comparability of the numbers tested to find 1 P. falciparum case.

Table 3

Number of people tested to find 1 P. falciparum case from January 2018 and June 2020
Project year	Case detection approach	P. falciparum	Tested	Number of people tested to find 1 P. falciparum case^b
2018	Mobile malaria post	545	5,897	11
	Outreach	343	6,906	20
	Co-traveller investigation	46	604	13
2019	Mobile malaria post	136	12,839	94
	Outreach	170	19,693	116
	Co-traveller investigation	8	768	96
2020^a	Mobile malaria post	10	7,236	724
	Outreach	12	11,465	955
	Co-traveller investigation	---	71	---
	Active screening	---	348	---
Overall	Mobile malaria post	691	25,972	38
	Outreach	525	38,064	73
	Co-traveller investigation	54	1,443	27
	Active screening	---	348	---
^a Until June 2020 ^b Number of all tests conducted in a specified period divided by number of P. falciparum cases detected during the specific period

Contribution to accelerated elimination of P. falciparum malaria in project areas

Figure 4 shows the absolute number of positive malaria cases by species and the number of people tested through project service delivery sites (Fig. 4 : Number of P. falciparum positives, P. vivax positives and people tested within the project from January 2018 to June 2020). The number of P. falciparum cases decreased by 93% from the period January to June 2018 to the same period in 2020 with testing rates staying constant. Between January and June 2018, 7.4 P. falciparum cases were detected for every P. vivax case. This ratio has consistently inversed since June 2018, and between January and June 2020, only 0.6 P. falciparum cases were detected for every P. vivax case which is a significant achievement on the path to P. falciparum malaria elimination. Between January and June 2020, only 22 P. falciparum cases were detected in project areas of Stung Treng and Ratanakiri, while no P. falciparum cases have been detected in project areas of Preah Vihear since October 2019.

Taking into account data reported by associated health facilities and VMWs in the project area, MMWs under this project have contributed to testing 52% of all people tested and detecting 40% of all P. falciparum cases and 74% of community P. falciparum cases between January 2018 to June 2020.

This case study describes the results from implementing a tailored package of active case detection approaches to reach remote populations in border areas in three provinces in north-eastern Cambodia between January 2018 and June 2020.

Results show service delivery sites efficiently reached and tested people with each service delivery site testing a monthly average of 62 people in 2020. Cases were managed with high quality, with all positive cases either treated or referred as per national guidelines. Operational challenges (stock-outs of treatment, changing population movement patterns, hard to reach operational area) did not lastingly impact the overall quality of service delivery. On the contrary, efficiency of service delivery was improved over the project period through tactical optimization of timing and location of service delivery and possibly an increase of trust between MMWs and local communities. Responsive monitoring and evaluation systems in combination with strong community relationships can contribute to tangible improvements of project delivery and efficiency of services.

We showed that tailored active case detection approaches indeed resulted in reaching the target population (9) and detecting P. falciparum cases. Our results also show that while the group most at risk of being infected is still males over 15 years, people travel to forests in mixed-age and -gender groups. Programs need to maintain sufficient stock of paediatric formulations and effective referrals of pregnant women to health centres.

Comparing proactive case detection approaches, while mobile malaria posts and outreach activities are equally efficient in reaching people with similar daily averages considering operationally active days, mobile malaria posts needed to test less people on average to find 1 P. falciparum case indicating a more effective case detection strategy. The importance of well-functioning mobile malaria posts in any malaria elimination strategy has been previously reported (22). Nevertheless, outreach activities remain invaluable in order to reach less accessible places and achieve testing targets set by the CNM. Further, outreach activities are beneficial in providing health education and establishing the presence of MMWs in remote communities as they regularly interact with the target population, pass on malaria messages and distribute LLIN/ LLIHNs. Through these interactions, members of target communities are encouraged to actively seek out health services from MMWs or other service providers when they develop symptoms. Previous studies have pointed out the importance of community trust in service providers for health seeking behaviour (23, 24).

MMWs under this project significantly contributed to maintaining high testing rates and detecting new P. falciparum cases in the area. Using a tailored package of approaches has been shown to be an effective way to find remaining P. falciparum cases and contribute to the acceleration of P. falciparum malaria elimination.

Remaining Challenges

Maintaining intensified efforts to find last P. falciparum cases and prevent re-establishment

Using tailored packages of active case detection approaches in combination with the community-based passive case detection system will remain a key approach for the final phases of P. falciparum malaria elimination. However, detecting and treating the last remaining P. falciparum cases and preventing re-establishment will require intensified efforts and resources: We showed that the number of people tested to find 1 P. falciparum case has been steadily increasing over the last three years, requiring health workers to remain motivated among decreasing positivity yields. While testing fatigue among the health work force and target population has not been observed yet, targeted health promotion and social and behaviour change communication activities need to be implemented to maintain awareness. The CNM has recently started to implement case investigations for every P. falciparum case within 3 days of notification to determine if the infection was acquired locally. If it was, a focus investigation is conducted within 14 days of detection which helps determine the set of interventions to be undertaken (25). Intensified efforts conducting tailored active case detection and surveillance activities including case and focus investigations will need to be maintained until malaria is eliminated.

Addressing the asymptomatic reservoir and the low sensitivity of RDTs

Previous studies in the region have shown high proportions of asymptomatic P. falciparum carriers among the risk population (18, 26). This population is usually missed by conventional RDTs with data showing that sensitivity of RDTs compared to polymerase chain reaction (PCR) in asymptomatic carriers could be as low as 18% (19). Sensitivity of RDTs among symptomatic cases has been reported to be insufficient as well, especially in cases with low parasitemia (19, 27, 28). Hence, many P. falciparum carriers, symptomatic and asymptomatic, are missed by field diagnostics while they might still constitute an ongoing reservoir of further transmission. Diagnostic tools with higher sensitivity than conventional RDTs have been trialled, but either were not adopted as in the case mobile PCR laboratories that could have been used in field settings (29) or were shown not to sufficiently increase sensitivity as in the case of high-sensitivity RDTs (25). Recently, researchers and policymakers in Cambodia discussed novel tools to further accelerate P. falciparum malaria elimination and considered approaches not depending on testing. While mass drug administration and mass screening and treatment approaches were ruled out for various reasons, trialling malaria prophylaxis in forest workers was deemed a promising idea to be explored in the short term (25).

Shifting focus to P. vivax malaria

As P. falciparum malaria steadily declines, P. vivax malaria has been becoming more prominent. While the epidemiology of the two malaria species is similar in terms of geography, transmission pattern and risk groups (30), treatment of P. vivax poses a particular challenge to elimination efforts in terms of liver hypnozoites causing periodic relapses. National guidelines recommend primaquine radical cure which requires prior testing for glucose-6-phosphate dehydrogenase (G6PD)-deficiency to ensure safe drug administration (14). While point-of-care tests for G6PD deficiency have been trialled (31), the lack of adoption and availability of these tests prevents the routine use of primaquine radical cure at primary health facilities (30). Distinct approaches for targeting P. vivax malaria need to be developed alongside the continued delivery of tailored P. falciparum interventions.

We have presented a successful approach to implementing tailored active case detection strategies in forested border areas in north-eastern Cambodia. Key components of the project success were a combination of proactive and reactive case detection activities tailored to the local target population and context, operational flexibility, strong relationships with local communities, close supervision and quality assurance of service delivery and responsive systems that were able to adapt to changing circumstances. While some challenges remain that need to be addressed before malaria elimination can be reached, we believe that this is an effective approach that can be transferred to similar settings in other areas of the GMS targeting malaria elimination.

MMW – Mobile malaria worker

p. falciparum – Plasmodium falciparum

p. vivax – Plasmodium vivax

GMS – Greater Mekong Subregion

RAI – Regional Artemisinin-resistance Initiative

RAI2E – Regional Artemisinin-resistance Initiative 2 Elimination

EDAT – Early diagnosis and effective treatment

CNM – National Center for Parasitology, Entomology and Malaria Control

VMW – Village malaria worker

ACT - Artemisinin-based combination therapy

LLINs/ LLIHNs – Long lasting insecticide-treated nets and hammock nets

RDT – Rapid diagnostic test

MIS – Malaria information system

PCR – Polymerase chain reaction

G6PD – Glucose-6-phosphate dehydrogenase

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This project was funded was funded by The Global Fund to Fight AIDS, Tuberculosis and Malaria under the RAI2E program. The funders had no role in the data collection and analysis, decision to publish, or preparation of the manuscript.

Authors' contributions

AS conducted the data analysis and drafted the manuscript. All authors made significant contributions to the revisions of the manuscript and approved the submission of the final version.

Acknowledgements

The authors would like to thank the staff of the National Centre for Parasitology, Entomology and Malaria Control, the Provincial Health Districts, the Operational Districts and the Health Centres for their strong collaboration during the implementation of this project. Specifically, we thank Dr. Huy Rekol, the Director of the National Centre for Parasitology, Entomology and Malaria Control, Dr. Ung Ratana, Director of Ratanakiri Provincial Health Department, Dr. Ung Soviet, Director of Stung Treng Provincial Health Department and Dr Koung Lo, Director of Preah Vihear Provincial Health Department. We thank all other implementing partners of the Regional Artemisinin Initiative for their contributions. We thank Médecins Sans Frontières for their support during the period of stock-outs in 2018. This project would not have been possible without the dedicated work of all project staff and mobile malaria workers who supported and continue to support the implementation of this project.

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Eliminating Plasmodium Falciparum Malaria: Results From Tailoring Active Case Detection Approaches to Remote Populations in Forested Border Areas in North-eastern Cambodia

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Background

Objectives

Approach

Project setting

Project design

Translation into practice

Implementation And Results

Data collection and analysis

Delivery of tailored active case detection approaches

Operational set-up

Efficiency of service delivery

Quality of case management

Reaching the target population

Effectiveness of case detection approaches in detecting P. falciparum cases

Discussion

Remaining Challenges

Addressing the asymptomatic reservoir and the low sensitivity of RDTs

Conclusions

Abbreviations

Declarations

Ethics approval and consent to participate

Consent for publication

Availability of data and materials

Competing interests

Funding

Authors' contributions

Acknowledgements

References

Status:

Journal Publication

Version 1