**5. Utilize surveillance as a core intervention linked to results-based funding (SCI-RBF) to achieve rapid and effective action in actual transmission foci**

#### **5.1. Development of an innovative information (surveillance) system to eliminate emerging incurable malaria**

In 2015–2016, our research team worked in two provinces in Vietnam (**Figure 5**) to field test a surveillance/information system envisioned in a background paper written for the BMGF [43]. We partnered with National Institute of Malariology, Parasitology and Entomology (NIMPE) and the Phu Yen Provincial Health Department (PHD) to develop and pilot test the information system linked to a pay-for-performance system. We also developed concepts to target forest malaria transmission foci and/or people traveling to these locations with effective integrated prevention and treatment.

#### *5.1.1. 2015 results*

We defined transmission locations, intervention usage, risk groups/factors and desired interventions. This was first done with a household survey of the identifiable malaria patients from the most recent 100 cases and a sample of nearby houses (**Table 3**). This table illustrates total cases and risk by work-type and that the reported use of program-provided long lasting insecticidal nets (LLINs) in actual transmission areas was very low [9]. For example, most malaria cases (49%) were coming from paper plantations, but farmers and charcoal producers were at higher risk (75 and 80%, respectively). LLIN and overall treated nets in use were only 6 and 19%, respectively. Households with malaria were ~three-fold less likely to use treated nets, Odds Ratio 3.2; p < 0.01) [76]. The actual transmission locations were determined by where people reported sleeping one to two weeks before they developed fever (malaria incubation period). The lack of transmission at the village level was confirmed by the lack of malaria patients who remained in the village during the incubation time for malaria.

These results were next confirmed and extended through geographic reconnaissance of sleeping sites of malaria patients (**Figure 6**) [8, 9, 44]. At each sleeping site, GPS coordinates, with images the sleeping structure and the nets being used (if any), were captured (**Figure 6**). The pictures were used to validate self-reported data (e.g., **Figures 7** and **8**). Interviews revealed forest rangers reported taking partial malaria treatment when ill, malaria infection was common and lack of prevention measures for work in the forest at night. Based on this information, we suspected this population was the primary transmission reservoir in this area, similar to that recently reported from forest rangers in a nearby province [66].

**Figure 6** illustrates that actual forest transmission locations were readily identifiable; 80% were accessible within one hour by motorcycle. For the remaining 20%, the optimal placement of malaria posts to access those at risk was determined. The primary factors for low treated net use were the fact that 92% desired a hammock net (with few provided) and 83% desired a zip-type hammock net [76]. The hard-type LLINs that were provided were a type that was strongly disliked by 85% of those surveyed. Of the forest-goers surveyed, 89% reported they would be willing to use mosquito repellent and 91% malaria prophylaxis [76]. Based on these results, we believe the provision of nets of a type that people want to use, net retreatment

**Figure 5.** Vietnam study districts in Quang Tri (Hung Hoa District) and Phu Yen Provinces (Dong Xuan District) (blue

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outlined areas).

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In conclusion, we urge donors and NMCEPs to help supporting security forces take action. This should include first to make sure security forces are using appropriate prevention and treatment packages. GMS security forces absolutely can directly support elimination operations. They best understand the mobile and migrant populations (MMPs) and terrain of the remaining forest in the region, understand military planning and have a structured workforce in many of the challenging areas. We call on donors to provide the leadership and funding by making sure that security forces are not a transmission reservoir and are engaged in the fight against malaria.

**5. Utilize surveillance as a core intervention linked to results-based funding (SCI-RBF) to achieve rapid and effective action in actual** 

**5.1. Development of an innovative information (surveillance) system to eliminate** 

In 2015–2016, our research team worked in two provinces in Vietnam (**Figure 5**) to field test a surveillance/information system envisioned in a background paper written for the BMGF [43]. We partnered with National Institute of Malariology, Parasitology and Entomology (NIMPE) and the Phu Yen Provincial Health Department (PHD) to develop and pilot test the information system linked to a pay-for-performance system. We also developed concepts to target forest malaria transmission foci and/or people traveling to these locations with effective

We defined transmission locations, intervention usage, risk groups/factors and desired interventions. This was first done with a household survey of the identifiable malaria patients from the most recent 100 cases and a sample of nearby houses (**Table 3**). This table illustrates total cases and risk by work-type and that the reported use of program-provided long lasting insecticidal nets (LLINs) in actual transmission areas was very low [9]. For example, most malaria cases (49%) were coming from paper plantations, but farmers and charcoal producers were at higher risk (75 and 80%, respectively). LLIN and overall treated nets in use were only 6 and 19%, respectively. Households with malaria were ~three-fold less likely to use treated nets, Odds Ratio 3.2; p < 0.01) [76]. The actual transmission locations were determined by where people reported sleeping one to two weeks before they developed fever (malaria incubation period). The lack of transmission at the village level was confirmed by the lack of

malaria patients who remained in the village during the incubation time for malaria.

that recently reported from forest rangers in a nearby province [66].

These results were next confirmed and extended through geographic reconnaissance of sleeping sites of malaria patients (**Figure 6**) [8, 9, 44]. At each sleeping site, GPS coordinates, with images the sleeping structure and the nets being used (if any), were captured (**Figure 6**). The pictures were used to validate self-reported data (e.g., **Figures 7** and **8**). Interviews revealed forest rangers reported taking partial malaria treatment when ill, malaria infection was common and lack of prevention measures for work in the forest at night. Based on this information, we suspected this population was the primary transmission reservoir in this area, similar to

**transmission foci**

*5.1.1. 2015 results*

**emerging incurable malaria**

56 Towards Malaria Elimination - A Leap Forward

integrated prevention and treatment.

**Figure 5.** Vietnam study districts in Quang Tri (Hung Hoa District) and Phu Yen Provinces (Dong Xuan District) (blue outlined areas).

**Figure 6** illustrates that actual forest transmission locations were readily identifiable; 80% were accessible within one hour by motorcycle. For the remaining 20%, the optimal placement of malaria posts to access those at risk was determined. The primary factors for low treated net use were the fact that 92% desired a hammock net (with few provided) and 83% desired a zip-type hammock net [76]. The hard-type LLINs that were provided were a type that was strongly disliked by 85% of those surveyed. Of the forest-goers surveyed, 89% reported they would be willing to use mosquito repellent and 91% malaria prophylaxis [76]. Based on these results, we believe the provision of nets of a type that people want to use, net retreatment


a Cases of malaria/people interviewed.

b Number reporting any net reported being used at forest sleeping site/number interviewed in work type.

c Number reporting any net reported being used at forest sleeping site/total interviewed.

<sup>d</sup>Program was providing annual net retreatment accounting for the difference between 6% for LLIN.

**Table 3.** Malaria-risk populations and bed net use in Phu Yen Province, Vietnam in 2015.

for self-purchased products, repellent availability, along with on-going education and use monitoring will enable high usage of an integrated prevention package.

Lastly, a concept was developed for a malaria elimination task force (METF) led and implemented by PHD staff, implemented by mobile malaria workers (MMWs). The METF should routinely have challenge-solving workshops with NMCEP staff to improve the quality of data and responses.

**Figure 6.** Baseline malaria transmission location map with insecticide treated net (ITN) usage in Phu Yen Province, 2015. The turquoise color represents 4700 households. In 2016, provincial health records showed 4.3 treated nets per household. Dots are the forest sleeping locations 1–2 weeks earlier, including 95% of 2015 cases. The color of the dots reveals very low use of nets in actual transmission areas, despite very high coverage in the village (where there was no transmission). The light purple circles are transmission foci, defined here as two cases within a 1 km radius, which

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Despite very high household insecticide-treated net coverage, their use in risk areas is very low. Forest transmission sites are identifiable and targetable directly and/or at forest pathway points. The described transformative smart-phone based information technology will facilitate rapid malaria elimination allowing near real-time monitoring to improve the quality and targeting of interventions. Urgent action must be taken to improve the selection of interventions of products benefitting people at risk and for those working in actual transmission areas.

Based in part on our work in 2015–2017, Phu Yen Province saw the largest drop (89%) in malaria of any province in the region of the south-central coast and central highlands in this time frame. In 2016, as cases decreased, the cases spatially clustered into two areas to prioritize (pink dots in **Figure 9**). In our study district, malaria reduction is striking. In 2017, only 13 cases were reported, compared to 52 (**Figure 9**), 133, 292, and 291 in the years 2016–2013, respectively, a

*5.1.2. Conclusions*

captured 80% of all cases.

*5.1.3. Broader impact*

**Figure 6** also illustrates the smart-phone based information system, which greatly improved our ability to conduct near-real time data capture and quality control from Hanoi, while the team was working in the field. Information was captured using a smartphone app with the data fed into an on-line server when Internet access was available to the field staff. Ona.io server, KoboToolbox (http://www.kobotoolbox.org/) and other systems are inexpensive, easy-to-program/use, powerful new tools for the fight against malaria.

In **Table 4**, we outline the interventions we believe are needed for rapid malaria elimination. We illustrate linking of successful execution of the interventions to incentive pay, which was successfully pilot tested. Data captured from each intervention can constitute "surveillance as core intervention (SCI)." Incentive payments can be linked to the smartphone-captured data following quality checks. We believe surveillance as an intervention with results-based funding (SCI-RBF) will motivate staff to make sure patients complete antimalarial treatment and effectively intervene in transmission foci (both of which are still largely lacking).

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**Figure 6.** Baseline malaria transmission location map with insecticide treated net (ITN) usage in Phu Yen Province, 2015. The turquoise color represents 4700 households. In 2016, provincial health records showed 4.3 treated nets per household. Dots are the forest sleeping locations 1–2 weeks earlier, including 95% of 2015 cases. The color of the dots reveals very low use of nets in actual transmission areas, despite very high coverage in the village (where there was no transmission). The light purple circles are transmission foci, defined here as two cases within a 1 km radius, which captured 80% of all cases.

Lastly, a concept was developed for a malaria elimination task force (METF) led and implemented by PHD staff, implemented by mobile malaria workers (MMWs). The METF should routinely have challenge-solving workshops with NMCEP staff to improve the quality of data and responses.

#### *5.1.2. Conclusions*

for self-purchased products, repellent availability, along with on-going education and use

**Figure 6** also illustrates the smart-phone based information system, which greatly improved our ability to conduct near-real time data capture and quality control from Hanoi, while the team was working in the field. Information was captured using a smartphone app with the data fed into an on-line server when Internet access was available to the field staff. Ona.io server, KoboToolbox (http://www.kobotoolbox.org/) and other systems are inexpensive,

In **Table 4**, we outline the interventions we believe are needed for rapid malaria elimination. We illustrate linking of successful execution of the interventions to incentive pay, which was successfully pilot tested. Data captured from each intervention can constitute "surveillance as core intervention (SCI)." Incentive payments can be linked to the smartphone-captured data following quality checks. We believe surveillance as an intervention with results-based funding (SCI-RBF) will motivate staff to make sure patients complete antimalarial treatment and

monitoring will enable high usage of an integrated prevention package.

Number reporting any net reported being used at forest sleeping site/total interviewed.

**Table 3.** Malaria-risk populations and bed net use in Phu Yen Province, Vietnam in 2015.

**Main work type**

Paper plantation

Agarwood harvesting

Charcoal production

Timber harvesting

a

b

c

Cases of malaria/people interviewed.

**n Percent** 

58 Towards Malaria Elimination - A Leap Forward

**interviewed**

**Number of malaria cases**

**Percent total malaria (n = 93)**

Farmer 16 8% 12 13% 75% 80% 80% 0% 38% Trapper 16 8% 6 6% 38% 44% 25% 13% 6%

Hunter 3 2% 3 3% 100% 0% 0% 0% 0% Other 3 2% 2 2% 67% 67% 67% 0% 0% **Total or mean 190 100% 93 100% 49% 68%**<sup>c</sup> **19% 32% 6%**

Number reporting any net reported being used at forest sleeping site/number interviewed in work type.

<sup>d</sup>Program was providing annual net retreatment accounting for the difference between 6% for LLIN.

**Percent risk malariaa**

94 49% 44 47% 47% 65% 11% 41% 2%

39 21% 14 15% 36% 95% 15% 36% 8%

10 5% 8 9% 80% 70% 0% 50% 0%

9 5% 4 4% 44% 33% 11% 11% 0%

**Nets currently used (n = 186)**

> **At least a treated net typed**

**Any netb**

**Net types currently used (n = 189)**

> **At least a LLIN type**

**At least a zip hammock type**

easy-to-program/use, powerful new tools for the fight against malaria.

effectively intervene in transmission foci (both of which are still largely lacking).

Despite very high household insecticide-treated net coverage, their use in risk areas is very low. Forest transmission sites are identifiable and targetable directly and/or at forest pathway points. The described transformative smart-phone based information technology will facilitate rapid malaria elimination allowing near real-time monitoring to improve the quality and targeting of interventions. Urgent action must be taken to improve the selection of interventions of products benefitting people at risk and for those working in actual transmission areas.

#### *5.1.3. Broader impact*

Based in part on our work in 2015–2017, Phu Yen Province saw the largest drop (89%) in malaria of any province in the region of the south-central coast and central highlands in this time frame. In 2016, as cases decreased, the cases spatially clustered into two areas to prioritize (pink dots in **Figure 9**). In our study district, malaria reduction is striking. In 2017, only 13 cases were reported, compared to 52 (**Figure 9**), 133, 292, and 291 in the years 2016–2013, respectively, a


**Figure 7.** Example use of smart phone technology to capture information, images and video linked to GPS coordinates. A. Smart phones with good data coverage are becoming ubiquitous, Ona.oi smartphone data capture; B. Ona.io internet interface; C. Transmission focus map with global positioning system (GPS) coordinates of sleeping locations of malaria patients; D-F. Pictures linked to GPS coordinates for quality control, D. Forest ranger station, E. How the net should look not how did it look, F. Tag on the net to confirm if it is an LLIN or not; G. Example of key data. All will allow for near-real time monitoring of intervention quality with regularly updated maps to allow malaria elimination staff, donors, and key leaders to understand what is happening where and when, from anywhere with internet access for the first time—this technology "changes the game".

96% reduction from baseline. The malaria lead for Phu Yen Province reported our contribution, noting the health staff "operated more effectively" during and following our project.

#### **5.2. New approaches to "leap forward" to achieve more rapid malaria elimination**

#### *5.2.1. Development of a "Red-to-Green, Keep-it-Green" information system to achieve high adherence with both integrated vector control and treatment interventions*

Based on what we learned in 2015, an information system using the "Red light-Green light" approach, as envisioned by Alan Magill, was developed. Based on 2015 case mapping (**Figure 6**), a simple system was developed to prioritize actual transmission areas for targeting interventions (**Figure 10**). The dot in each circle represents prevention status and the triangle treatment status in each focus. Those presented are treated net usage (dots) and time to ACT treatment (triangles), but must be enhanced to include both an integrated prevention and treatment package (**Table 5**).

One can visualize the low usage of treated bed nets (red dots). In addition, all but two sites are within one hour by motorcycle of a health center for ACT treatment (green triangles). The green triangles also reflect that most of the forest transmission sites are directly accessible for both responses to new cases and for on-going monitoring. The sites with an orange and a red triangle need proper placement of malaria posts or mobile malaria workers to capture people

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**Figure 8.** Image evidence of LLIN usage. A–C represent probable use and D-F, non-use. Note in E, chickens inside.

The map on the bottom of **Figure 10** illustrates perfect, 100% "Green" status. We believe 60–70% "Green" targets will be sufficient to rapidly eliminate malaria. These maps can be

going deeper into the forest.

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**Figure 8.** Image evidence of LLIN usage. A–C represent probable use and D-F, non-use. Note in E, chickens inside.

96% reduction from baseline. The malaria lead for Phu Yen Province reported our contribution,

**Figure 7.** Example use of smart phone technology to capture information, images and video linked to GPS coordinates. A. Smart phones with good data coverage are becoming ubiquitous, Ona.oi smartphone data capture; B. Ona.io internet interface; C. Transmission focus map with global positioning system (GPS) coordinates of sleeping locations of malaria patients; D-F. Pictures linked to GPS coordinates for quality control, D. Forest ranger station, E. How the net should look not how did it look, F. Tag on the net to confirm if it is an LLIN or not; G. Example of key data. All will allow for near-real time monitoring of intervention quality with regularly updated maps to allow malaria elimination staff, donors, and key leaders to understand what is happening where and when, from anywhere with internet access for the first time—this

Based on what we learned in 2015, an information system using the "Red light-Green light" approach, as envisioned by Alan Magill, was developed. Based on 2015 case mapping (**Figure 6**), a simple system was developed to prioritize actual transmission areas for targeting interventions (**Figure 10**). The dot in each circle represents prevention status and the triangle treatment status in each focus. Those presented are treated net usage (dots) and time to ACT treatment (triangles), but must be enhanced to include both an integrated prevention

noting the health staff "operated more effectively" during and following our project.

**5.2. New approaches to "leap forward" to achieve more rapid malaria elimination**

*5.2.1. Development of a "Red-to-Green, Keep-it-Green" information system to achieve high* 

*adherence with both integrated vector control and treatment interventions*

and treatment package (**Table 5**).

technology "changes the game".

60 Towards Malaria Elimination - A Leap Forward

One can visualize the low usage of treated bed nets (red dots). In addition, all but two sites are within one hour by motorcycle of a health center for ACT treatment (green triangles). The green triangles also reflect that most of the forest transmission sites are directly accessible for both responses to new cases and for on-going monitoring. The sites with an orange and a red triangle need proper placement of malaria posts or mobile malaria workers to capture people going deeper into the forest.

The map on the bottom of **Figure 10** illustrates perfect, 100% "Green" status. We believe 60–70% "Green" targets will be sufficient to rapidly eliminate malaria. These maps can be


a Screen: screening with new highly sensitive rapid diagnostic tests (hsRDTs); BCC: behavior change communication; IT-ASSBA: insecticide treatment around sleeping, sitting, sleeping and bathing areas (most sleeping structures are huts without walls).

b These are example costs; true costs will be estimated in the field in Cambodia from May–August 2018. Some of these costs are currently provided as travel incentives and monthly stipends for field staff which are not focused on results; the estimates do not include commodities.

**Table 4.** Example of surveillance as an intervention with results-based funding (SCI-RBF) for the first year of implementation.

regularly updated in an on-line information system for donors, national programs and implementers to monitor progress near real-time.

#### *5.2.2. Mitigation of forest malaria transmission with more effective and complete prevention/ treatment packages*

We believe a more comprehensive prevention and treatment package targeting malaria transmission foci, and the people working or traveling there, will have rapid impact, especially when those constituting the primary transmission reservoir are targeted. Pf must be the priority as this species is causing the public health emergency. Both Pf and Pv are transmitted by the same vector species. Pv remains a challenge for cure because of the dormant liver stage (hypnozoites). All of the prevention interventions will also be efficacious for control of Pv, and will drive down transmission in parallel. Pv residual transmission will often remain when Pf has been eliminated. The same resources can be used to mop up residual Pv transmission, which will also ensure that Pf has been truly eliminated.

Durnez and Coosemans [78] (**Figure 11**). Additional tools are available—achieving adherence with all prevention tools is the critical challenge, which we believe can be addressed with

Each of these measures has partial efficacy—they must be used in combination with adherence monitoring to achieve high effectiveness. With all drugs soon to be lost, a focus must be placed on use of an integrated vector control package. New vector control products are also in the pipeline, which should be added when effectiveness is demonstrated.

**Figure 9.** Actual malaria transmission locations by year in Dong Xuan District, Phu Yen Province, Vietnam. Please note the marked clustering of the pink dots as malaria transmission decreased in 2016 to 52 cases from 133 in 2015. Based in part on our effort to demonstrate actual transmission locations and lack of treated nets at these sites, malaria cases

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continued to decrease to 13 cases in 2017 (a 96% reduction from baseline in 2013-2014).

>90% using a treated net Complete treatment and follow-up

Treated clothing Targeted malaria posts to forest entry points Mosquito repellent Mobile malaria workers to access hot-spots Safer sleeping, sitting and bathing areas Screening with highly sensitive RDTs

**Table 5.** Immediately available interventions for integrated prevention and treatment in transmission foci.

**Prevention Treatment**

In **Table 5**, immediately available prevention and treatment measures are outlined. We believe the use of treated nets can be greatly increased in actual transmission areas with smart phone

SCI-RBF (see Section 5.1.1).

ITNs are the cornerstone for malaria prevention worldwide, but have inadequate efficacy (e.g., in areas of unstable malaria transmission, 62 and 43% efficacy is reported with no or untreated nets for Pf prevention, respectively [77]). ITNs lack effect when not in use as illustrated by Preparing for the Next Global Threat: A Call for Targeted, Immediate Decisive Action… http://dx.doi.org/10.5772/intechopen.78261 63

**Figure 9.** Actual malaria transmission locations by year in Dong Xuan District, Phu Yen Province, Vietnam. Please note the marked clustering of the pink dots as malaria transmission decreased in 2016 to 52 cases from 133 in 2015. Based in part on our effort to demonstrate actual transmission locations and lack of treated nets at these sites, malaria cases continued to decrease to 13 cases in 2017 (a 96% reduction from baseline in 2013-2014).


Each of these measures has partial efficacy—they must be used in combination with adherence monitoring to achieve high effectiveness. With all drugs soon to be lost, a focus must be placed on use of an integrated vector control package. New vector control products are also in the pipeline, which should be added when effectiveness is demonstrated.

**Table 5.** Immediately available interventions for integrated prevention and treatment in transmission foci.

regularly updated in an on-line information system for donors, national programs and imple-

**Table 4.** Example of surveillance as an intervention with results-based funding (SCI-RBF) for the first year of imple-

Total \$ 449,696

Screen: screening with new highly sensitive rapid diagnostic tests (hsRDTs); BCC: behavior change communication; IT-ASSBA: insecticide treatment around sleeping, sitting, sleeping and bathing areas (most sleeping structures are huts

These are example costs; true costs will be estimated in the field in Cambodia from May–August 2018. Some of these costs are currently provided as travel incentives and monthly stipends for field staff which are not focused on results;

We believe a more comprehensive prevention and treatment package targeting malaria transmission foci, and the people working or traveling there, will have rapid impact, especially when those constituting the primary transmission reservoir are targeted. Pf must be the priority as this species is causing the public health emergency. Both Pf and Pv are transmitted by the same vector species. Pv remains a challenge for cure because of the dormant liver stage (hypnozoites). All of the prevention interventions will also be efficacious for control of Pv, and will drive down transmission in parallel. Pv residual transmission will often remain when Pf has been eliminated. The same resources can be used to mop up residual Pv transmission,

ITNs are the cornerstone for malaria prevention worldwide, but have inadequate efficacy (e.g., in areas of unstable malaria transmission, 62 and 43% efficacy is reported with no or untreated nets for Pf prevention, respectively [77]). ITNs lack effect when not in use as illustrated by

*5.2.2. Mitigation of forest malaria transmission with more effective and complete prevention/*

**No. Intervention/item Descriptiona Cost/formb Cost/intervention/**

Full interview and interventions at initial patient encounter

new nets, BCC

3.1 Foci response (Village) Screen & treat, treat nets,

3.2 Foci response (Forest) Screen & treat, treat nets,

4 Foci monitoring Screen & treat, treat nets,

Document adherence and late treatment success

new nets, BCC, IT-ASSBA

Screen & treat, treat nets, new nets, BCC, IT-ASSBA

new nets, BCC, IT-ASSBA

Screen & treat, treat nets, new nets, BCC, IT-ASSBA

Routine visits to document diagnosis, treatment, prevention and reporting

**caseb**

\$ 4.15 \$ 4.15 \$ 4149

\$ 20.47 \$ 51 \$ 51,182

\$ 3.75 \$ 113 \$ 67,500

\$ 15.26 \$ 305 \$ 122,054

\$ 30.51 \$ 610 \$ 61,027

\$ 7.63 \$ 76 \$ 76,284

\$ 3.75 \$ 38 \$ 37,500

\$ 16.00 \$ 2500 \$ 30,000

**Results-based funding (cost/year)b**

menters to monitor progress near real-time.

the estimates do not include commodities.

which will also ensure that Pf has been truly eliminated.

*treatment packages*

1 Rapid case report, initial investigations and initial response

62 Towards Malaria Elimination - A Leap Forward

2 Treatment plan and follow-up

3.3 Foci response (Cross-border)

5 Forest entry point/ work place monitoring

6 On-going provider quality monitoring

a

b

without walls).

mentation.

Durnez and Coosemans [78] (**Figure 11**). Additional tools are available—achieving adherence with all prevention tools is the critical challenge, which we believe can be addressed with SCI-RBF (see Section 5.1.1).

In **Table 5**, immediately available prevention and treatment measures are outlined. We believe the use of treated nets can be greatly increased in actual transmission areas with smart phone

military, including contributing to the interruption of Pf transmission [20]. The literaturebased evidence of efficacy of permethrin-treated clothing is presented in **Table 2**. Based on the available data and the growing body of evidence that those working in the forest at night in the GMS are a significant transmission reservoir, we believe treated uniforms/clothing should be scaled up as rapidly as possible. We believe retreatment of clothing, self-purchased nets and insecticide treatment around sleeping, sitting and bathing areas (IT-ASSBA) should be routine in hot-spots. Re-treatment will also allow for on-going education and monitoring. Treated netting when used with partial coverage in sleeping areas has been shown to reduce *An. dirus* (the main forest vector in the GMS) bites by 50% in Eastern Vietnam (Marchand R, unpublished

figure is also often red in the GMS because of lack of use of ITNs in risk areas (see **Figures 6** and **10**).

**Figure 11.** Protection "gap" when only indoor insecticide-based vector control measures are applied. *Anopheles* mosquitoes bite between 6 PM and 6 AM. A "gap" exists while people are not sleeping (A) and for people conducting night-time outdoor activities (B) (courtesy of Durnez and Coosemans [78]). Additional note: even the green part of the

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data). Some efficacy has also been seen for other insecticide-treated products [79, 80].

single application in Eastern Vietnam (Marchand R, unpublished data).

Topical insect repellent clearly prevents mosquito bites when used correctly, especially for outdoor biting mosquitoes such as *An. dirus* that are otherwise hard to control with traditional indoor methods (ITN, IRS); however, getting people to regularly use the product in risk areas (be adherent or compliant) is the challenge, probably being the primary factor leading to a lack of efficacy in recent trials in the GMS [81]. Locally available DEET-containing repellent was well accepted and prevented *An. dirus* bites in forest transmission areas all night in a

Prompt, complete and correct treatment is the cornerstone for malaria therapy. The effective ACT regimen should be used for both Pf and Pv blood stages. Primaquine in standard dosages should be used for Pf gametocytes and Pv hypnozoites in countries where these doses are already being used as standard of care (e.g., Vietnam) or low-dose [82] for Pf gametocytes in areas where there are safety concerns. We believe that all patients in the GMS should have visits on days 28 and 42 to detect late-treatment failure, as well as to have malaria patients and their work groups be transmission-stopping ambassadors. In addition, improved tools are just becoming available to

**Figure 10.** "Red-to-Green, Keep-it-Green" information system (see https://ConsortiumHA.org); (a) the blue circles are transmission areas to prioritize; here classified as 2 cases within a 1 km radius, which captured 80% of cases. Within the blue circles, a small circle represents the prevention package and a triangle represents the treatment package. The top of this figure represents the actual status of Dong Xuan District, Phu Yen Province, Vietnam in 2015. The prevention package was only the use of a treated net or not, and the treatment package was only time to access effective malaria treatment. As you can see, treated net use is poor, but all but two triangles are green, illustrating that all but two transmission foci are within one hour of a health center by motorcycle. This also means they are directly accessible for interventions, both when a new case occurs and for on-going monitoring of use of malaria elimination tools. (b) the theoretical desired 100% green status. 100% will never by achieved – we believe perhaps 60-70% usage of an integrated prevention and treatment package will be enough to rapidly reduce transmission.

monitoring. The SCI-RBF will also allow iterative testing and improvement of methods until high usage is achieved, both with ITNs and an integrated vector control package. There is now direct evidence of substantial efficacy of permethrin-treated uniforms in the Cambodian Preparing for the Next Global Threat: A Call for Targeted, Immediate Decisive Action… http://dx.doi.org/10.5772/intechopen.78261 65

**Figure 11.** Protection "gap" when only indoor insecticide-based vector control measures are applied. *Anopheles* mosquitoes bite between 6 PM and 6 AM. A "gap" exists while people are not sleeping (A) and for people conducting night-time outdoor activities (B) (courtesy of Durnez and Coosemans [78]). Additional note: even the green part of the figure is also often red in the GMS because of lack of use of ITNs in risk areas (see **Figures 6** and **10**).

military, including contributing to the interruption of Pf transmission [20]. The literaturebased evidence of efficacy of permethrin-treated clothing is presented in **Table 2**. Based on the available data and the growing body of evidence that those working in the forest at night in the GMS are a significant transmission reservoir, we believe treated uniforms/clothing should be scaled up as rapidly as possible. We believe retreatment of clothing, self-purchased nets and insecticide treatment around sleeping, sitting and bathing areas (IT-ASSBA) should be routine in hot-spots. Re-treatment will also allow for on-going education and monitoring. Treated netting when used with partial coverage in sleeping areas has been shown to reduce *An. dirus* (the main forest vector in the GMS) bites by 50% in Eastern Vietnam (Marchand R, unpublished data). Some efficacy has also been seen for other insecticide-treated products [79, 80].

Topical insect repellent clearly prevents mosquito bites when used correctly, especially for outdoor biting mosquitoes such as *An. dirus* that are otherwise hard to control with traditional indoor methods (ITN, IRS); however, getting people to regularly use the product in risk areas (be adherent or compliant) is the challenge, probably being the primary factor leading to a lack of efficacy in recent trials in the GMS [81]. Locally available DEET-containing repellent was well accepted and prevented *An. dirus* bites in forest transmission areas all night in a single application in Eastern Vietnam (Marchand R, unpublished data).

Prompt, complete and correct treatment is the cornerstone for malaria therapy. The effective ACT regimen should be used for both Pf and Pv blood stages. Primaquine in standard dosages should be used for Pf gametocytes and Pv hypnozoites in countries where these doses are already being used as standard of care (e.g., Vietnam) or low-dose [82] for Pf gametocytes in areas where there are safety concerns. We believe that all patients in the GMS should have visits on days 28 and 42 to detect late-treatment failure, as well as to have malaria patients and their work groups be transmission-stopping ambassadors. In addition, improved tools are just becoming available to

monitoring. The SCI-RBF will also allow iterative testing and improvement of methods until high usage is achieved, both with ITNs and an integrated vector control package. There is now direct evidence of substantial efficacy of permethrin-treated uniforms in the Cambodian

prevention and treatment package will be enough to rapidly reduce transmission.

64 Towards Malaria Elimination - A Leap Forward

**Figure 10.** "Red-to-Green, Keep-it-Green" information system (see https://ConsortiumHA.org); (a) the blue circles are transmission areas to prioritize; here classified as 2 cases within a 1 km radius, which captured 80% of cases. Within the blue circles, a small circle represents the prevention package and a triangle represents the treatment package. The top of this figure represents the actual status of Dong Xuan District, Phu Yen Province, Vietnam in 2015. The prevention package was only the use of a treated net or not, and the treatment package was only time to access effective malaria treatment. As you can see, treated net use is poor, but all but two triangles are green, illustrating that all but two transmission foci are within one hour of a health center by motorcycle. This also means they are directly accessible for interventions, both when a new case occurs and for on-going monitoring of use of malaria elimination tools. (b) the theoretical desired 100% green status. 100% will never by achieved – we believe perhaps 60-70% usage of an integrated identify asymptomatic malaria carriers through active case detection (ACD). The BMGF funded the development of a highly sensitive rapid diagnostics test (hsRDT), which is specific for Pf [83]. It is much more sensitive than standard rapid diagnostic tests (RDT), but not as sensitive as PCR (which is probably not necessary) [84, 85]. Alere (www.alere.com, now Abbott) has made these hsRDTs commercially available for \$0.95/each; approvals in GMS are in process. The same company also markets a malaria antibody-based RDT for both Pf and Pv [86]. The usefulness of these new tools can be rapidly demonstrated during scale-up; the hsRDT will hopefully obviate the need for mass drug administration [87]. Both of these new RDTs should facilitate defining risk populations.

Viet Dang and Thinh Duc Ngo). Drs. Nam Dinh Nguyen, Tuong Trinh Dinh, Global Fund, Hanoi, Vietnam provided technical support, data analysis and illustration preparation. Dr. Hung Pham, Consortium for Health Action, Savage, MN, USA and Hanoi, Vietnam provided project leadership and coordination. Dr. Gerard Kelly, Research School of Population Health, Canberra, Australia for geographic information system (GIS) planning and support. We also would like to thank Michael MacDonald for critical review of this chapter. We thank Ms. Tuyen Pham for providing illustration editing for this chapter. This work was supported in part by funding from the US Department of Defense. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the US Department of Defense, nor the US or Vietnamese Government. Much of this work was inspired by the late Alan Magill (former Director of Malaria, Bill & Melinda Gates Foundation).

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**Acronyms**

ACD active case detection

ADB Asian Development Bank

BCC behavior change communication BMGF Bill & Melinda Gates Foundation

ConsortiumHA Consortium for Health Action

GIS Geographic Information System

hsRDT highly sensitive rapid diagnostic test IHRs International Health Regulations

IT-ASSBA insecticide treatment around sleeping, sitting and bathing areas

GMS Greater Mekong Subregion GPS global positioning system

IRS indoor residual spraying

ITN insecticide treated nets

MDR multidrug-resistant

LLIN long lasting insecticidal nets

CR cluster randomized trial

DoD Department of Defense

GF Global Fund

ACT artemisinin-based combination therapy

CDC US Center for Disease Control and Prevention

DHAPP Defense HIV/AIDS Prevention Program

ERAR emergency response to artemisinin resistance

If the package of available tools does not rapidly stop malaria transmission, other more aggressive tools can be added as they become available [85]. Currently available drugs are problematic for prophylaxis—primaquine and doxycycline require daily dosing; doxycycline has already been widely used along the Vietnam border—its current efficacy is unknown. Mefloquine is poorly tolerated and its use for prophylaxis may accelerate its demise. Tafenoquine [88, 89] and RTS,S malaria vaccine [90] should be accelerated to play a role for prevention in the region.

The last remaining parasites will be the most drug-resistant—alternative regimens are urgently needed. Tafenoquine [91] (unpublished observations for Pf), azithromycin and methylene blue [92–95] are currently under recognized, but could also play a role in combination treatment when no alternatives remain, which may be very soon. New regimens should be urgently evaluated; all should be seven days, as some or all of the drugs will have short half-lives. With sevenday regimens, adherence will be very challenging. Hospitalization with appropriate incentives should become the norm to achieve very high treatment adherence in the near future, including the current three-day regimens in areas where outpatient treatment monitoring is not successful.
