After the World’s first attempt at eradicating the complicated disease malaria mainly through a single tool, a period of control set in where the aim was to reduce mortality through prompt and presumptive treatment of fevers with anti-malarials, particularly in young children. During this period in the 1980s and 1990s it was recognized that parasite-based diagnostic capabilities in the form of microscopy were limited, so in malaria endemic areas, it was worth providing inexpensive medicines like chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) to febrile children in order to save lives. When the fevers did not resolve, other illnesses explored.

The difficulty arose in identifying cases that did not offer clinical clues that they might be malaria. Today countries approaching malaria elimination face challenges, such as seen in Zanzibar where, “outdoor transmission, a large asymptomatic parasite reservoir and imported infections, require novel tools and reoriented strategies to prevent a rebound effect and achieve elimination.”[i] Here we examine the challenge of asymptomatic malaria infections.

Background

By 1998 when the Roll Back Malaria partnership formed, there had been enough research done so that the malaria community had a better arsenal of interventions including insecticide-treated bed nets, artemisinin-based combination therapy (ACT) and intermittent preventive treatment with SP during pregnancy. The Abuja Declaration of 2000 set a target of 80% coverage of these interventions by the year 2010.

While ACTs overcame the challenges of parasite resistance that had developed for the single drugs, CQ and SP, it cost several times more than those medicines. The need for easy-to-use, inexpensive, point-of-care diagnostics was recognized so that not only would ACTs be targeted only to parasitologically confirmed malaria cases, but also in the process, overuse and misuse would not contribute to parasite resistance of these new drugs.[ii] Unfortunately, the development and dissemination of antigen-based rapid diagnostic tests (RDTs), lagged behind the availability of ACTs meaning that health workers unfortunately continued their business as usual with presumptive treatment using ACTs. 

The benefits of RDTs were generally two-fold. First, they could be used by front-line, auxiliary and community-based health workers. Secondly, they tended to identify more cases than microscopy. The big challenge was convincing health workers to use them and trust the results, because the era of presumptive treatment had given these staff a false sense of confidence in their own clinical diagnostic abilities.

Although reaching the 2010 coverage targets has remained illusive for most endemic countries, there has been enough progress for major reductions in incidence (despite a recent upsurge).[iii] As the proportion of actual malaria cases among febrile illness patients declines, concern has risen that transmission might continue among people with subclinical or asymptomatic malaria. Here we explore the extent of this problem and new directions in parasitological testing needed to ensure continued progress toward elimination in each endemic country.

Understanding the Risk of Asymptomatic Malaria

Risk can relate to geographical, epidemiological, and socio-demographic factors as well as history of malaria interventions. Kenya has stratified the country by higher and lower malaria transmission areas. Even the higher areas are comparatively low compared to its higher transmission neighbors. Studying the prevalence of asymptomatic malaria in some of these higher transmission areas in the west of the country was seen as a way to better identify people at risk and learn about intervention effectiveness. An examination of apparently healthy children (no symptoms) revealed a Plasmodium falciparum malaria prevalence 36.0% (27.5%, 44.5%) by RDT and 22.3% (16.0%, 28.6%) by thick film microscopy.[iv] Living in a household with electricity was protective but the adjusted odds ratio of prevalence comparing households with and without indoor residual spray showed only borderline benefit. Unfortunately, in Zanzibar, asymptomatic malaria infection was not associated “with use of any vector control.”¹

A major challenge in detecting cases through routine health care systems is care seeking patterns of care seeking for fever. The 2018 World Malaria Report acknowledges that there are major equity challenges in care seeking wherein families with higher incomes, better education and living in urban areas are more likely to seek help for their febrile children that rural, poor and less educated families who would be more at risk. Care seeking without the signs of fever is more challenging. A dual strategy of enabling better service utilization as well as outreach to detect cases will be necessary to detect asymptomatic cases.³

In Burkina Faso, the prevalence of asymptomatic malaria infection in children under 5 years of age was estimated at 38.2% in 24 of its 70 health districts. Those at most risk for asymptomatic malaria infection included the following:[v]

• older children (48–59 vs < 6 months: OR: 6.79 [5.62, 8.22])
• children from very poor households (Richest vs poorest: OR: 0.85 [0.74–0.96])
• households located more than 5 km from a health facility (< 5 km vs ? 5 km: OR: 1.14 [1.04–1.25])
• localities with inadequate number of nurses (< 3 vs ? 3: 0.72 [0.62, 0.82]
• rural areas (OR: 1.67 [1.39–2.01])

Nine districts reported significantly higher risks (Batié, Boromo, Dano, Diébougou, Gaoua, Ouahigouya, Ouargaye, Sapouy and Toma. The researchers concluded that, “Such national spatial analysis should help to prioritize areas for increased malaria control activities.”

A study in Ghana found that, “children and pregnant women had higher prevalence of submicroscopic gametocytes (39.5% and 29.7%, respectively) compared to adults
(17.4%).”[vi]

An additional concern is emerging in terms of sharing of malaria parasite species between humans and primates, especially as urbanization and deforestation push these two populations into closer contact. For example Mapua and colleagues working in Central Africa Republic, “found the human malaria parasite P. ovale wallikeri in both asymptomatic humans and western lowland gorillas in Dzanga Sangha Protected Areas. Molecular analysis revealed that the genotype of the P. ovale wallikeri DNA found in a gorilla was genetically identical to that of a human isolate within the mt cytb and mt cox 1 genes, indicating potential human–ape transmission.”[vii] They noted similar sharing of parasites in the region between humans and chimpanzees.

Detecting and Responding to Asymptomatic Cases

WHO’s Framework for Malaria Elimination[viii] recognizes the important role of case detection and subsequent treatment as well as broader community level preventive responses around detected cases. In the context of elimination WHO notes that case detection “requires use of a diagnostic test to identify asymptomatic malaria infections.” WHO stresses that a case is a case, regardless of whether it is symptomatic or asymptomatic, as long as the diagnostic process confirms presence of malaria infection.

It is important to monitor Plasmodium parasitemia in areas where malaria transmission has declined and efforts to achieve malaria elimination are underway, such as Zambia, where 3,863 household members were tested.[ix] Only 2.6% were positive by either microscopy, RDT, or PCR. Of these, 48 (47%) had subpatent parasitemia, and 85% of those with subpatent parasitemia were asymptomatic. “Compared with individuals without parasitemia, individuals with subpatent parasitemia were significantly more likely to be aged 5–25 years.” The authors suggested that their findings pointed to the need for active or reactive case detection to identify asymptomatic individuals and thus better target individuals with subpatent parasitemia with appropriate malaria interventions.

WHO explains that active case detection (ACD) takes place in areas of limited or under-utilization of health care services.⁴ It may start with initial screening for symptoms, followed by appropriate parasitological laboratory confirmation. In low-transmission settings or as part of a focus investigation, “ACD may consist of testing of a defined population group without prior symptom screening (population-wide or mass testing) in order to identify asymptomatic infections.” Elimination cannot be achieved until even asymptomatic infections have stopped. The challenge is the expense of community-wide screening.

Reactive Case Detection (RCD), according to WHO, takes place in settings low transmission intensity where the few “occurring malaria cases are highly aggregated.”⁴ When a case is identified, usually through identification of an actual infected patient at a local clinic, the community where the patient comes from is visited and a “net is cast around the index case” where household members and neighbors within a selected radius are tested. In this process asymptomatic cases are also identified.

Our existing diagnostic tools may be inadequate. McCreesh and colleagues reported on subpatent malaria in Namibia that, “fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups.” This includes loop-mediated isothermal amplification (LAMP) using dried blood spots, which they tested.[x] Likewise from experience in a Zambian study, Kobayashi and co-researchers suggest, “more sensitive diagnostic tests or focal drug administration may be necessary to target individuals with subpatent parasitemia to achieve malaria elimination.”[xi]

Responses to detecting asymptomatic cases start at the individual level with prompt treatment of those found through RCD to be infected. Then focused preventive interventions such as distribution of insecticide treated bednets can be provided to those in the cluster or village. Follow-up would be needed for such ‘hot spots.’ 

On a broader basis we have Seasonal Malaria Chemoprevention (SMC) as practiced in Sahelian countries where during the peak transmission (rainy) season intermittent preventive treatment is given to children monthly by community health workers and volunteers. Of course, many of these children would be asymptomatic carriers and SMC could benefit the reduction of parasites in circulation. At present SMC focuses on pre-school aged children, but Thera and co-researchers stress the importance of reaching school aged children who are also often asymptomatic carriers.[xii]

Another intervention being tested for mass drug administration (MDA) use providing the community with ivermectin, a drug that has been highly effective in controlling filarial diseases and also found to kill mosquitoes who take a blood meal from a person who has recently taken it.[xiii] This strategy is still being tested, but again MDA means all community members, especially those with asymptomatic infection, would be reached.

A major question requires further research. To what extent do asymptomatic, submicroscopic and subpatent parasitemia contribute to continued malaria transmission? Another question is how can we address malaria infection in other primates? We know that scientists recommend targeting of malaria elimination interventions based on mapping of these infections.⁵ We therefore need to study the actual transmission potential of this phenomenon.

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[i] Björkman A, Shakely D, Ali AS, Morris U, Mkali H, Abbas AK, Al-Mafazy A-W, Haji KA, Mcha J, Omar R, Cook J, Elfving K, Petzold M, Sachs MC, Aydin-Schmidt B, Drakeley V, Msellem M and Mårtensson A. From high to low malaria transmission in Zanzibar—challenges and opportunities to achieve elimination. BMC Medicine (2019) 17:14, https://doi.org/10.1186/s12916-018-1243-z

[ii] Global Malaria Programme. Universal access to malaria diagnostic testing – An operational manual. World Health Organization. November 2011 (rev. February 2013). https://www.who.int/malaria/publications/atoz/9789241502092/en/

[iii] Global Malaria Programme. World malaria report 2018. World Health Organization. 19 November 2018. https://www.who.int/malaria/publications/world-malaria-report-2018/en/

[iv] Peprah S, Tenge C, Genga IO, Mumia M, Were PA, Kuremu RT, Wekes WN,  Sumba PO, Kinyera T, Otim T, Legason ID, Biddle J, Reynolds SJ, Talisuna AO, Biggar1 RJ, Bhatia K, Goedert JJ, Pfeiffer RM, Mbulaiteye SM. A Cross-Sectional Population Study of Geographic, Age-Specific, and Household Risk Factors for Asymptomatic Plasmodium falciparum Malaria Infection in Western Kenya. The American Journal of Tropical Medicine and Hygiene, Volume 100, Issue 1, Jan 2019, p.54-65. DOI: https://doi.org/10.4269/ajtmh.18-0481.

[v] Ouédraogo M, Samadoulougou S, Rouamba T, Hien H, Sawadogo JEM Tinto H, Alegana VA, Speybroeck N and Kirakoya?Samadoulougou F. Spatial distribution and determinants of asymptomatic malaria risk among children under 5 years in 24 districts in Burkina Faso. Malaria Journal 2018; 17:460 https://doi.org/10.1186/s12936-018-2606-9

[vi] Lamptey H, Ofori MF, Kusi KA, Adu B, Owusu-Yeboa E, Kyei-Baafour E, Arku AT, Bosomprah S, Alifrangis M, Quakyi IA. The prevalence of submicroscopic Plasmodium falciparum gametocyte carriage and multiplicity of infection in children, pregnant women and adults in a low malaria transmission area in Southern Ghana. Malar J. 2018 Sep 17;17(1):331. doi: 10.1186/s12936-018-2479-y.

[vii] Mapua MI, Hans-Peter Fuehrer HP, Petrželková KJ, Todd A, Noedl H, Qablan MA, and Modrý D. Plasmodium ovale wallikeri in Western Lowland Gorillas and Humans Central African Republic. Emerging Infectious Disease journal. Volume 24, Number 8—August 2018. https://wwwnc.cdc.gov/eid/article/24/8/18-0010_article

[viii] Global Malaria Programme. A framework for malaria elimination. ISBN 978-92-4-151198-8. World Health Organization 2017, http://www.who.int/malaria/publications/atoz/9789241511988/en/

[ix] Kobayashi T, Kanyangarara M, Laban NM, Phiri M, Hamapumbu H, Searle KM, Stevenson JC, Thuma PE, Moss WJ and the Southern Africa International Centers of Excellence for Malaria Research. Characteristics of Subpatent Malaria in a Pre-Elimination Setting in Southern Zambia. The American Journal of Tropical Medicine and Hygiene, 10 December 2018, DOI: https://doi.org/10.4269/ajtmh.18-0399

[x] McCreesh P, Mumbengegwi D, Roberts K, Tambo M, Smith J, Whittemore B, Kelly G, Moe C, Murphy M, Chisenga M, Greenhouse B, Ntuku H, Kleinschmidt I, Sturrock H, Uusiku P, Gosling R, Bennett A, Hsiang MS. Subpatent malaria in a low transmission African setting: a cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, Namibia. Malar J. 2018 Dec 19;17(1):480. doi: 10.1186/s12936-018-2626-5.

[xi] Kobayashi T, Kanyangarara M, Laban NM, Phiri M, Hamapumbu H, Searle KM, Stevenson JC, Thuma PE, Moss WJ, For The Southern Africa International Centers Of Excellence For Malaria Research.Characteristics of Subpatent Malaria in a Pre-Elimination Setting in Southern Zambia. Am J Trop Med Hyg. 2018 Dec 10. doi: 10.4269/ajtmh.18-0399. [Epub ahead of print]

[xii] Thera MA, Konea AK, Tangaraa B, Diarraa E, Niarea A, Dembeleb A, Sissokoa MS, Doumboa OK. School-aged children based seasonal malaria chemoprevention using artesunate-amodiaquine in Mali. Parasite Epidemiology and Control 3 (2018) 96–105. https://doi.org/10.1016/j.parepi.2018.02.001

[xiii] Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong’o BO, Chen T, Bousema T, Slater HC, Waterhouse D, Bayoh NM, Gimnig JE, Samuels AM, Desai MR, Phillips-Howard PA, Kariuki SK, Wang D, Ward SA, ter Kuile FO. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine. www.thelancet.com/infection Published online March 27, 2018 http://dx.doi.org/10.1016/S1473-3099(18)30163-4

Goodluck Tesha, Zahra Mkomwa, Jasmine Chadewa, Lusekelo Njoge, Abdallah Lusasi, Dunstan Bishanga, Chonge Kitojo, Erik Reaves, George Greer of the USAID Boresha Afya Project, the Tanzanian Ministry of Health, and the US President’s Malaria Initiative shared experiences on the role of malaria case management in pre-elimination efforts at the 2018 Annual Meeting of the American Society of Tropical medicine and Hygiene. Their results are seen below.

The 5-year USAID Boresha Afya project works in 1,817 facilities in the seven regions of the Lake/Western Zone, where malaria prevalence is high. Since 2016, Boresha Afya has collaborated with the National Malaria Control Program to support the goal of reducing the malaria case fatality rate to below 1% by 2020 by:

• Promoting universal access to early diagnosis and prompt treatment
• Providing preventive therapies to vulnerable groups

In the last 15 years, malaria transmission has been cut in half, dropping from about 33% to less than 7.5%. Over the last three malaria indicator surveys, the number of regions with extremely low malaria prevalence (<1%) increased from one (2008) to seven (2016). The percentage of the population living in low-transmission areas (<10% prevalence) increased from 31% in 2000 to 49% in 2015.

The intervention trained providers on quality testing using malaria rapid diagnostic tests (mRDTs). Training focused on conducting quality malaria microscopy examinations.

In addition, the team stratified malaria burden using GIS mapping and introduced malaria service and data quality improvement through a malaria dashboard. Community outreach programs were formed in remote areas.

Due to mRDT availability, more suspected malaria cases are tested before malaria treatment is administered. Per national guidelines, all pregnant women should be tested for malaria on their first visit to the clinic. All project regions have met or exceeded the national 80% testing rate target (see Figure 5).

In conclusion, to move toward malaria elimination, Boresha Afya will focus on ensuring more suspected cases are tested at facility level. Prompt treatment positive cases will then follow. Performing more community outreach should increase access to malaria case management in remote areas. Using GIS mapping will rapidly target services.

This poster is made possible by the support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of Jhpiego and do not necessarily reflect the views of USAID or the United States Government.

The Sahel Malaria Elimination Initiative (SaME) has been launched, but builds on a long history of cooperation in the region. Efforts by eight Sahelian countries to share lessons and strategies mirrors the Elimination Eight group on the opposite end of the continent.

The Roll Back Malaria (RBM) Partnership to End Malaria announced that in Dakar on 31^st August 2018, the health “ministers from Burkina Faso, Cabo Verde, Chad, Mali, Mauritania, Niger, Senegal and The Gambia established a new regional platform to combine efforts on scaling up and sustaining universal coverage of anti-malarials and mobilizing financing for elimination.” The group plans a fast-track introduction of “innovative technologies to combat malaria and develop a sub-regional scorecard that will track progress towards the goal of eliminating malaria by 2030.” This will build on the existing country scorecard that has been developed and implemented by AMLA2030 for all countries in the region and tracks roll out of key malaria and health interventions. The Sahel Malaria Elimination Initiative will be hosted by the West African Health Organization, a specialised agency of the Economic Community of West African States (ECOWAS).

RBM explains that while the eight countries will work together, they do not have a homogenous epidemiological picture or experience with malaria programming. The Sahel experiences 20 million annual malaria cases, according to RBM, and “the Sahel region has seen both achievements and setbacks in the fight against the disease in recent years.” These eight have a highly variable malaria experience. Burkina Faso and Niger continue to be among the countries with high malaria burdens. Cabo Verde is on target for malaria free status by 2020. The Gambia, Mauritania and Senegal are reorienting their national malaria program towards malaria elimination. A benefit of this epidemiological and programmatic diversity is that countries can learn important lessons from each other.

The SaME Initiative will use the following main approaches to accelerate the combined efforts towards the attainment of malaria elimination in the sub-region:³

• Regional coordination
• Advocacy to keep malaria elimination high on the development and political agenda
• Sustainable financing mechanisms
• Cross-border collaboration and ensuring accountability
• Fast-track the introduction of innovative and progressive technologies
• Re-enforcing the Regional regulatory mechanism for quality of malaria commodities and introduction of new tools.
• Establish malaria observatory, regional surveillance, and best practice sharing

Collaboration across borders on vector control is an example of needed regional coordination. According to Thomson et al., climate variations have the potential to significantly impact vector-borne disease dynamics at multiple space and time scales. Another challenge to vector control in the region is the issue of how mosquitoes repopulate areas after an extended dry season. Huestis et al. examined the response of Anopheles coluzzii and Anopheles gambiae to environmental cues in season change in the Sahel.

In addition to a history of cooperation, Sahelian countries share a unique malaria intervention, Seasonal Malaria Chemoprevention (SMC) that as the name implies, built on the reality of highly seasonal transmission in the region. SMC grew out of over five years of research in several African settings to test the effect of what was originally termed Intermittent Preventive Treatment for Infants (and later children) or IPTi.

Like IPT for pregnant women, SMC would be given monthly for at least 3-4 months, but unlike IPTp, SMC would consist of a combination two medicines, amodiaquine plus sulfadoxine-pyrimethamine (AQ+SP), which required a three daily doses (SP alone as used in IPTp consists on one dose). SMC could not therefore, be delivered effectively as a clinic-based intervention, but “should be integrated into existing programmes, such as Community Case Management and other Community Health Workers schemes.” Access to SMC by pre-school aged children as delivered by CHWs was found to be more equitable than sleeping under an LLIN. SMC has been recommended for school-age children, a neglected group that bears a substantial burden of malaria.

Closely linked to surveillance is modeling the spatial and temporal variability of climate parameters, which is crucial to tackling malaria in the Sahel. This requires reliable observations of malaria outbreaks over a long time period. To date efforts are mainly linked to climate variables such as rainfall and temperature as well as specific landscape characteristics. Other environmental and socio-economic factors that are not included in this mechanistic malaria model.

The Sahel Malaria Elimination initiative offers a unique collaborative opportunity for countries to improve on the quality of proven interventions like SMC and test and take to scale new strategies like school-based malaria programs. Regional coordination can produce better, timelier and longer-term surveillance and better understanding of and actions against malaria vectors. Readers will surely be anticipating the publishing of the regular progress malaria elimination scorecards as promised by SaME leadership.

Mobile migrant populations present a special challenge for malaria control and elimination efforts. Nguyen Ha Nam and colleagues* (Nguyen Xuan Thang, Gary Dahl, James O’Donnell, Vashti Irani, Sara Canavati, Jack Richards, Ngo Duc Thang, and Tran Thanh Duong) presented their study of this group at the recent Malaria World Congress. They are also sharing what they learned below.

Mobile Migrant Populations (MMPs) are a key population for containing the spread of malaria in the border areas between Cambodia and Vietnam. The number of imported cases in Viet Nam in 2017. 12,5% of such cases caught in Binh Phuoc and Dak Nong provinces and all of them came from Cambodia. The provinces bordering Cambodia and Vietnam have been had the highest malaria transmission intensity. This borders are frequented by MMPs who have proven difficult to target for surveillance and malaria control activities.

Mobile Outreach Teams (MOTs) provide a potential approach to target malaria elimination activities for MMPs who may not be strongly supported by the regular village-based and clinic-based health services. This work describes the implementation of MOTs in Binh Phuoc and Dak Nong Provinces, which are high-risk regions along the Viet Nam-Cambodia border. These activities were conducted as part of the Regional Artemisinin-resistance Initiative (RAI) in 2017. Each MOT was comprised of 2 Commune Health Staff and 1 Village Health Worker (VHW) from the village nearest to the outreach area.

In the first phase of the pilot, 3 communes of 2 districts in Binh Phuoc and 2 communes of 1 district in Dak Nong with highest malaria cases reported from NIMPE are selected as targeted areas. The Objectives were to …

• Design/tailor Mobile Outreach Information Education and Communication/Behaviour change communication (BCC/ IEC) Toolkit
• Intensify case detection and quality management by increasing the coverage of diagnostics and treatment for hard to reach populations
• Strengthen outreach to high-risk and under-served populations through MOT scouting activities to locate unreached Mobile Communities and map their locations
• Link MMPs with health facilities and Village Health Workers

All MOT members were provided with smartphones and were trained on how to use the EpiCollect5 app to track malaria cases, record mapping information and upload real-time reports of these malaria cases. MOTs conducted 5-day outreach activities every month. These activities began with scouting out locations of the MMP communities.

Once located, the MOTs geo-tagged the location of the community, conducted a short epidemiological survey on the community and screened for malaria using Rapid Diagnostic Tests and blood smear microscopy. Active malaria cases were provided with treatment according to the National guidelines, and Long Lasting Insecticidal Nets were distributed based on results of diagnosis and the survey.

This action has led to increased diagnosis and treatment of hard to reach MMPs with increased access by those communities to malaria services. Improved understanding and increased use of malaria prevention practices hard to reach MMP communities/households. Mapped of previously unreached MMP Communities and unofficial border crossing points with malaria transmission hotspots and highly frequented crossing identified. The number of MMPs were monitored by MOTs were 2,699 accounting for 5.18% of the population in the project sites (2,699/52,095).

These screened MMPs were almost located along the border among project communes in Bu Gia Map National Forest where have a lot of unofficial border crossers, timber camp communities, and other revolving communities. 1,977 targeted people were tested for malaria. This number was achieved 73.25% of mobile migrant people (1,977/2,699). This work highlights how MOTs can target the previously unreached populations of MMPs to strengthen malaria surveillance and active case responses to reduce malaria transmission in Viet Nam.

A system of real-time data collection of malaria cases from VHWs and MOTs using mobile phone uploads was established. Border screening and tracking hard to reach communities is a useful approach to implement to identify imported cases; however, it is labor-intensive, and misses subjects crossing at unofficial borders due to limited working time of MOTs (5 days a month).

Positive cases in Binh Phuoc province are maintained for keeping track after receiving treatment due to no confirmed cases detected in targeted communes in Dak Ngo province, though these communes mainly have numerous transient timber camps moving in deep forests, and highly mobile border-crossers moving between regions and countries frequently. Future work will combine routine support from District health staff and expand the role of VHWs with motorbike provision for each MOT in order to not only to improve their quality outreach activities but also develop stronger Active Case Detection in the next phase of the project.

*Team members represent the National Institute of Malariology, Parasitology and Entomology, Hanoi, Viet Nam; Health Poverty Action, London, UK; and the Burnet Institute, Melbourne, Australia.

References

• Kheang ST, Lin MA, et al. Malaria Case Detection Among Mobile Populations and Migrant Workers in Myanmar: Comparison of 3 Service Delivery Approaches. 2018
• Shannon Takala-Harrison,a Christopher G. Jacob, et al. Independent Emergence of Artemisinin Resistance Mutations Among Plasmodium falciparum in Southeast Asia. 2014.
• Imwong M, Hien TT, et al. Spread of a single multidrug resistant malaria parasite lineage (PfPailin) to Vietnam. 2017.
• Richard J Maude,corresponding author Chea Nguon, et al. Spatial and temporal epidemiology of clinical malaria in Cambodia 2004–2013. 2014.
• Imwong M, Nguyen TN, et al.The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand–Myanmar border areas, Cambodia, and Vietnam. 2015.
• Hannah Edwards, Sara E. Canavati, et al. Novel Cross-Border Approaches to Optimise Identification of Asymptomatic and Artemisinin-Resistant Plasmodium Infection in Mobile Populations Crossing Cambodian Borders. 2015.

Viet Nam is among the Asia-Pacific countries focusing on eliminating malaria. Mapping helps target malaria interventions. Nguyen Xuan Thang and colleagues (James O’Donnell, Vashti Irani, Leanna Surrao, Ricardo Ataide, Josh Tram, An Le, Sara Canavati, Tran Thanh Duong, Tran Quoc Tuy, Gary Dahl, Gerard Kelly, Jack Richards, Ngo Duc Thang) presented their pilot mapping efforts at the Malaria World Congress in Melbourne recently and below share their experiences with us.

Viet Nam is focused on eliminating malaria by 2030. Viet Nam saw a 73% reduction in cases between 2013 and 2017 (NIMPE data), yet border provinces still have a high burden of malaria. However, some provinces still have a high burden of malaria. To achieve malaria elimination, it is essential to deploy targeted interventions in these locations.

Spatial Decision Support Systems (SDSS) can be used by National Malaria programs to integrate geographic elements in the management of malaria cases and facilitate targeted malaria interventions in these high-risk settings.

The objective of this work was to pilot a SDSS system for Binh Phuoc and Dak Nong Provinces in Viet Nam to facilitate ongoing surveillance and targeted malaria, as part of the Regional Artemisinin-resistance Initiative (RAI). This objective was achieved by:

• 

  Collecting data with cell phones

  Collecting baseline GIS data at household level and environmental characteristics associated with the area;

• Establishing a routine data collection system that will be reported by mobile medical staff by mobile phone;
• Integrating this data to form a spatial decision support system (SDSS);
• Using the SDSS system for direct reporting to malaria control programs that provided strategic solutions for the prevention of disease spread and the elimination of malaria

In Phase 1, a household and mapping survey was conducted in collaboration with commune, district and village health workers. Epicollect5 software was used on smartphones with GPS functionality to record mapping information (latitude and longitude) and general information on household members. During Phase 1, 10,506 households were surveyed and data was aggregated in a custom Geographic Information System (GIS) database.

The majority of the surveyed individuals were of the Kinh ethnicity (19,282; 35.4%), followed by M’Nong (4,669; 8.6%) and Mong (3,359; 6.2%). Data related to malaria among mobile populations were included in the GIS as a means to identify and describe groups at high risk for malaria e.g. forest-goers. The survey data were reviewed, cleaned and matched using the ID numbers, then aggregated with relevant administrative boundary data and linked on ArcGIS 10.2 software. This database is located in a custom GIS system and can be visualized as a spatial transmission model to support appropriate decision-making

Phase 2 focused on ongoing surveillance with rapid case reporting and responses. Malaria cases diagnosed at public and local health facilities were entered into the system by Commune Health Officials. Village Health Workers were immediately notified and went to the patient’s home to undertake case investigation including further household mapping and active case detection activities. The Viet Nam National Institute of Malariology was also notified, and organized local officials to carry out an investigation into the sources of transmission (i.e. ‘hotspots’) and to implement timely interventions.

When the cases were identified, Village Health Workers went to the patient’s home to undertake operational procedures including geographic exploration, household mapping to identify the location and to identify the list of affected households. They also collected this data on EpiCollect5. Collated information on cases, transmission point, zoning of the target villages allowed for early detection of malaria outbreaks. The National Institute of Malariology can also issue guidelines when the hotspots are identified and when disease outbreaks occur

These activities are ongoing. In conclusion, a custom GIS database was developed using a household survey in Binh Phuoc and Dak Nong province of Viet Nam. Malaria cases were mapped to identify hotspots of malaria transmission and enable further active case detection and targeted interventions. This established GIS database aims to support routine case notification and to enhance the role of surveillance for active case detection and responses to achieve malaria elimination.

The authors are affiliated with the National Institute of Malariology, Parasitology, Entomology (NIMPE), Viet Nam; Burnet Institute, Australia; and Health Poverty Action, UK. Contact: xuanthang.nimpe@gmail.com

Two things we need to note about the list of 20 diseases that the World Health Organization and partners classify as Neglected Tropical Diseases (NTDs). First, diseases like Rabies, Snakebite/envenoming, and Leprosy, while certainly more common in the tropics now, have in the past been global in distribution. Secondly some of the diseases have not been neglected. Onchocerciasis or river blindness has been the focus of a global partnership since 1975, and transmission in the America’s and much of the Sahel in Africa has been halted. Elimination of Dracunculiasis or Guinea Worm has also been the subject of many World Health Assembly Resolutions, and concerted effort has brought the number of cases down from 3.5 million in 1986 to 30 in 2017.  What is more to the point about these diseases is that they affect neglected people, the poor and vulnerable in remote rural areas or urban slums.

Still when we can compare NTD control programs with the rise of major disease control efforts like the Global Fund to fight AIDS, Tuberculosis and Malaria, the President’s Emergency Program For AIDS Relief, the President’s Malaria Initiative, World Bank Malaria Booster Program, Global A Vaccine Initiative among others, we can see that the global community has been able to focus major financial resources on a few diseases.  Now with the Sustainable Development Goals, that focus expanded from infectious to Non-Communicable Diseases.  It is natural therefore to fear that tropical health problems that are responsible for major loss of life and economic capacity will not be adequately addressed.

Based on the World Health Organization’s 2020 Roadmap on NTDs, the London Declaration on NTDs recognized a “tremendous opportunity to control or eliminate at least 10 of these devastating diseases by the end of the decade” (i.e. by 2020). These include eradication of Guinea worm disease, and elimination by 2020 of lymphatic filariasis (LF), leprosy, sleeping sickness {human African trypanosomiasis) and blinding trachoma. In addition drug access programmes should help control by 2020 schistosomiasis, soil-transmitted helminthes (STH), Chagas disease, visceral leishmaniasis and river blindness (onchocerciasis).

Five of the diseases are notable in that they can either be controlled or eliminated through Mass Drug Administration (MDA) using Preventive Chemo-Therapy (PCT). This effort is aided by drug donation programs at the global level and community based MDA at the local level. Ten companies were signatories to the London Declaration and contributed to drug donation programs to achieve MDA. According to WHO,

Preventive chemotherapy is aimed at optimizing the largescale use of safe, single-dose medicines and offers the best means of reducing the extensive morbidity associated with four helminthiases (lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiases) (6). Additionally, the large-scale administration of azithromycin – a key component of the SAFE strategy for trachoma (that is, lid surgery (S), antibiotics to treat the community pool of infection (A), facial cleanliness (C) and environmental improvement (E)) – is amenable to close coordination and, in future, possibly co-administration with interventions targeted at helminthiases.

Targets for the 5 PCT diseases vary. The aim is to eliminate LF and Trachoma by 2020. Although the efforts against onchocerciasis have been running the longest, the refocus from control to elimination meant increasing the geographical scope of intervention, and now elimination may not be feasible until 2025.  With a focus mainly on the school aged and based populations, programs against schistosomiasis and STH talk of control, not elimination, although some endemic countries hope that elimination may be possible if the focus of these programs expands. So far, Togo is the only Sub-Saharan African country to have eliminated LF, and Ghana to have eliminated Trachoma.

Partnerships, funding and drug donations need to be strengthened if more countries are to join the ranks of Togo and Nepal.

Dr Pedro Alonso who directed the World Health Organization’s Global Malaria Program, has had several opportunities in the past two weeks to remind the global community that complacency on malaria control and elimination must not take hold as there are still over 400,000 deaths globally from malaria each year. At the Seventh Multilateral Initiative for Malaria Conference (MIM) in Dakar, Dr Alonso drew attention to the challenges revealed in the most recent World Malaria Report (WMR). While there have been decreases in deaths, there are places where the number of actual cases is increasing.

Around twenty years ago the course of malaria changed with the holding of the first MIM, also in Dakar and the establishment of the Roll Bank Malaria (RBM) Partnership. These were followed in short order by the Abuja Declaration that set targets for 2010 and embodied political in endemic countries, as well as major funding mechanisms such as the Global Fund to fight AIDS, TB and Malaria. This spurred what has been termed a ‘Golden Decade’ of increasing investment and intervention coverage, leading to decreasing malaria morbidity and mortality. The Millennium Development Goals provided additional impetus to reduce the toll of malaria by 2015.

On Facebook Live yesterday Dr Alonso talked about that ‘Golden Decade.’ There was a 60% decrease in mortality and a 40% decreases in malaria cases. But progress slowing down and we may be stalled at a crossroads. He noted that history show unless accelerate efforts, malaria will come back with a vengeance. Not only is renewed political leadership and funding, particularly from affected countries needed, but we also need new tools. Dr Alonso explained that the existing tools allowed 7m deaths be diverted in that golden decade, but these tools are not perfect. We are reaching limits on these tools such that we need R&D for tools to enable quantum leap forward. Even old tools like nets are threatened by insecticide resistance, and research on alternative safe insecticides is crucial.

Dr Alonso at MIM pointed to the worrying fact that investment in malaria overall peaked in 2013. Investment by endemic countries themselves has remained stable throughout and never gone reached $1 billion despite advocacy and leadership groups like the Africa Leaders Malaria Alliance. The 2017 WMR shows that while 16 countries achieved a greater that 20% reduction in malaria cases, 25 saw a greater that 20% increase in cases. The outnumbering of decreasing countries by increasing was 4 to 8 in Africa, the region with the highest burden of the disease. Overall 24 African countries saw increases in cases between 2015 and 2016 versus 5 that saw a decrease. A review of the Demographic and Health and the Malaria Information Surveys in recent years show that most countries continue to have difficulty coming close to the Abuja 2010 targets for Insecticide treated net (ITN) use, prompt and appropriate malaria case management and intermittent preventive treatment of malaria in pregnancy (IPTp).

The coverage gap is real. The WMR shows that while there have been small but steady increase in 3 doses of IPTp, coverage of the first dose has leveled off. Also while ownership of a net by households has increased, less than half of households have at least one net for every two residents.

In contrast a new form of IPT – seasonal malaria chemoprevention (SMC) for children in the Sahel countries has taken off with over 90% of children receiving at least one of the monthly doses during the high transmission season. Community case management is taking off as is increased use of rapid diagnostic testing. Increased access to care may explain how in spite of increased cases, deaths can be reduced. This situation could change rapidly if drug resistance spreads.

While some international partners are stepping up, we are far short of the investment needed. The Gates Foundation is pledging more for research and development to address the need for new tools as mentioned by Dr Alonso. A big challenge is adequate funding to sustain the implementation of both existing tools and the new ones when they come online. Even in the context of a malaria elimination framework, WHO stresses the need to maintain appropriate levels of intervention with case management, ITNs and other measures regardless of the stage of elimination at which a country or sub-strata of a country is focused.

Twenty years after the formation of RBM and 70 years after the foundation of WHO, the children, families and communities of endemic countries are certainly ready to beat malaria. The question is whether the national and global partners are equally ready.

The 7th Pan African Malaria Conference holds from 15-20 April 2017, Dakar, Senegal. The conference celebrates 20 years since the initial establishment of the Multilateral Initiative on Malaria (MIM) by the Tropical Disease Research Program and partners.

During the conference next week, staff from Jhpiego malaria projects in Burkina Faso, Liberia, Nepal, Madagascar and Cameroon will share oral and poster presentations to highlight their work. Below is a list along with the location numbers.

• Application d’un Audit de la Qualité des données (DQA) du paludisme dans le District Sanitaire de Kribi, Cameroun, SS-13 Oral
• Contribution des Agent de Santé Communautaire (ASC) à l’amélioration de la prévention et la prise en charge du paludisme dans le district de Kribi, Cameroun, B-40 Poster
• MOH’s effort in developing and implementing Quality Assurance plan (QAP) for Global Fund-supported antimalarial drugs: A case study of Nepal in the context of malaria elimination, C-107 Poster
• Community-Based Health Workers in Burkina Faso: Are they ready to take on a larger role to prevent malaria in pregnancy? D-115 Poster
• Contribution of Community-Based Health Workers (CBHWs) to Improving Prevention of Malaria in Pregnancy in Burkina Faso: Review of health worker perceptions from the baseline study D-118 Poster
• Malaria in Pregnancy: The Experience of MCSP in Liberia, D-140 Poster
• Improved Malaria Case Management of Under-Five Children: The Experience of MCSP-Restoration of Health Liberia project D-141 Poster
• Experiences and perceptions of care seeking for febrile illness among caregivers, pregnant women and health providers in eight districts of Madagascar D-142 Poster

Abstracts will be shared here on the day of each presentation for those unable to attend MIM. Also check Jhpiego at Exhibit Booth 148.

Global Health Day 2018 sponsored by the Johns Hopkins University Center for Global Health featured a poster presentation by several colleagues on Improving the efficacy of reactive screen-and-treat for malaria elimination in southern Zambia. Fiona Bhondoekhan, William Moss, Timothy Shields, Douglas Norris, Kelly Searle, Jennifer Stevenson, Harry Hamapumba, Mukuma Lubinda and Japhet Matoba (Southern Africa International Centers of Excellence in Malaria Research, the JHU Bloomberg School of Public Health, and the Macha Research Trust, Zambia) share their findings below.

Background: Malaria screen-and-treat (called Step D in Zambia) is a reactive case detection strategy in which cases detected at a health center trigger community health workers (CHWs) to screen for secondary malaria cases within a 140-meter radius of the index case household using PfHRP2 rapid diagnostic tests (RDTs). Few studies evaluated whether an evidence-based strategy using environmental features that characterize the immediate surroundings of a household, can improve the efficiency of secondary case identification.

Objective: This study utilized the Step D and extended the screening radius to 250-meters (termed Enhanced Step D or ESD) to assess which local environmental variables can guide CHWs to identify secondary cases more efficiently. As Zambia works toward eliminating malaria, more refined and targeted case detection strategies are required to find the untreated malaria cases that could serve as potentially asymptomatic sources of infection. This study can help guide and plan reactive case detection strategies in Zambia that allow community health workers/field teams to employ an evidence-based strategy to find malaria-positive secondary households situated near index case houses more efficiently.

Methods: Demographic information, malaria diagnosis, bed-net use and ownership, cooking energy source, and household floor material were obtained from surveys. Households were stratified into malaria positive and negative secondary households using RDT and qPCR results. ArcGIS was used to generate the following local environmental variables: screening radius (140 vs. 250-meters), number of animal pens within 100-meters, distance to nearest animal pen, distance and elevation difference between index and secondary houses, as well as the following large scale environmental variables: distance to main road and nearest stream category. Generalized estimating equations (GEE) estimated the cross-sectional effect for the difference in odds of a positive vs. negative secondary household for each predictor. For the secondary analysis GEE with the same model specifications was used to estimate the cross-sectional difference in odds of a positive vs. negative household for each environmental predictor. Model fit was evaluated with the Hosmer-Lemeshow goodness of fit test and significance was evaluated as a p-value of 0.05. Statistical analyses were carried out using STATA 14.2.

Results: Screening within the index households yielded an overall parasite prevalence of 8.6%, which was higher by qPCR (8.1%) than RDT (2.7%) as seen in Table 1. Secondary households had an overall parasite prevalence of 1.9% with similar differences by test used. Key results from regression analysis seen in Table 2 include a difference in prevalence according to screening radius as well as by proximity to the nearest stream. Secondary analysis produced similar results but showed statistically significant higher odds for households where animal pens were present.

Conclusion: Screening for secondary households within low-transmission setting in Zambia could be optimized by using both local-scale indicators such as the presence of animal pens and large-scale indicators such as streams as environmental guiding tools.

Acknowledgements: This research was supported in part the Bloomberg Philanthropies and the Johns Hopkins Malaria Research Institute, and the NIH-sponsored Southern and Central Africa ICEMR 2U19AI089680.

Concerning malaria elimination, “WHO grants this certification when a country has proven, beyond reasonable doubt, that the chain of local transmission of all human (emphasis added) malaria parasites has been interrupted nationwide for at least the past 3 consecutive years.” This target is challenging enough, but becomes more complicated when we consider that zoonotic transmission of malaria among monkeys and humans has been documented in Brazil and Southeast Asia. We cannot expect monkeys to sleep under bednets, so creative and realistic solutions are needed.

The Malaria Eradication Research Agenda (malERA) recognizes this problem. Plasmodium knowlesi, originally found in macaque monkeys in Southeast Asia has been dubbed the fifth human malaria due to its spread to people as deforestation has disturbed the habitat of the monkeys. In particular malERA addresses the challenge of understanding the upward trend of this malaria infection in that region and the need for better understanding of transmission dynamics and proper diagnosis.

The danger of P. knowlesi is heightened by difficulties in diagnosing it and distinguishing it from other malaria species. “Recently, the prevalence of human infection with a simian malaria parasite, P. knowlesi, has become an important issue in a wide area of Southeast Asia. The identification of this parasite by microscopy is very difficult because it resembles the P. malariae parasite. However, the symptoms caused by P. malariae and P. knowlesi are very different, with only P. knowlesi causing severe and life-threatening malaria” (Komaki-Yasuda et al.)

Reports from Brazil highlight another ‘simian hotspot.’ While P. Knowlesi represents monkey infections reaching humans, the opposite may have happened to establish a reservoir in the New World. “P. vivax lineages appearing to originate from Melanesia that were putatively carried by the Australasian peoples who contributed genes to Native Americans. Importantly, mitochondrial lineages of the P. vivax-like species P. simium are shared by platyrrhine monkeys and humans in the Atlantic Forest ecosystem, but not across the Amazon, which most likely resulted from one or a few recent human-to-monkey transfers.”  But looking even further back in natural history, Escalante and colleagues found, “compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia.”

A recent study in this area found the worrying results that, “The low incidence of cases and the low frequency of asymptomatic malaria carriers investigated make it unlikely that the transmission chain in the region is based solely on human hosts, as cases are isolated one from another by hundreds of kilometers and frequently by long periods of time, reinforcing instead the hypothesis of zoonotic transmission.”

In Africa, Linda Duval and co-researchers, who found P. falciparum in blood samples from two chimpanzees belonging to two different subspecies, warn that, “If malignant malaria were eradicated from human populations, chimpanzees, in addition to gorillas, might serve as a reservoir for P. falciparum,”

It appears that the dynamics between monkeys, malaria and humans has a long history. Even once certified malaria-free countries face the threat of imported malaria from people crossing borders. Now we must recognize that the threat may already live within borders. So since existing malaria interventions to protect humans from malaria cannot be applied to monkeys, accelerated research on the genetics of the parasite and the mosquito is needed to prevent both primate groups from getting malaria.