Copyright © 2016 Means et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.                   
The attached file is the published version of the article

Arianna Rubin Means

Charles Mwandawiro

DA Bundy

David Rollinson

DB Elkins

Judd L. Walson

Julie Jacobson

K Massa

Kristjana Ásbjörnsdóttir

LS Stephenson

M Albonico

M Bradley

MB De Rochars

MJ Beach

P Hotez

Patrick J. Lammie

R Anderson

RM Anderson

Tim Littlewood

PLoS Neglected Tropical Diseases

PubMed

Crossref

Sustaining Progress towards NTD Elimination: An Opportunity to Leverage Lymphatic Filariasis Elimination Programs to Interrupt Transmission of Soil-Transmitted Helminths

Copyright © 2016 Means et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.                   
The attached file is the published version of the article.NHM Repositor

Means, AR

Asbjornsdottir, K

Mwandawiro, C

Rollinson, D

Jacobson, J

Littlewood, T

Walson, JL

Natural History Museum Repository

VIEWPOINTSSustaining Progress towards NTD Elimination:An Opportunity to Leverage LymphaticFilariasis Elimination Programs to InterruptTransmission of Soil-Transmitted HelminthsArianna Rubin Means1,2, Kristjana Ásbjörnsdóttir1,2, Charles Mwandawiro3,David Rollinson2, Julie Jacobson4, Tim Littlewood2, Judd L. Walson2,5*1 Department of Global Health, University of Washington, Seattle, Washington, United States of America,2 The DeWorm3 Project, The Natural History Museum of London, London, United Kingdom, 3 Eastern andSouthern Africa Centre of International Parasite Control, Kenya Medical Research Institute, Nairobi, Kenya,4 Neglected Tropical Disease Team, Bill & Melinda Gates Foundation, Seattle, Washington, United States ofAmerica, 5 Departments of Global Health, Medicine, Pediatrics, and Epidemiology, University ofWashington, Seattle, Washington, United States of America*walson@uw.eduIn light of the unprecedented momentum to control or eliminate ten neglected tropical diseases(NTDs) by 2020, the NTD community is at a crossroads of opportunity. Efforts to eliminatelymphatic filariasis (LF) using mass drug administration (MDA) platforms have dramaticallyand simultaneously increased the number of individuals treated for soil-transmitted helminths(STHs) in many areas, owing to overlaps in endemicity and drug efficacy. A concomitantreduction in STH infection raises the possibility of moving beyond current World HealthOrganization (WHO) morbidity control guidelines to actual disease elimination for STHs [1].We identify specific rationale, opportunities, and challenges associated with leveraging existingLF elimination platforms for the purpose of interrupting STH transmission.Over 1,500,000,000 people globally are infected with STHs, including roundworm (Ascaris lum-bricoides), whipworm (Trichuris trichiura), and hookworm species (Necator americanus and Ancy-lostoma duodenale). STHs are transmitted when infected persons shed eggs in feces that thencontaminate soil or water and are ingested by or penetrate the skin of others. An individual’s wormburden, or the intensity of their infection, is directly related to their risk of STH-associated morbid-ity. Moderate to heavy STH infections are associated with diarrhea, malnutrition, chronic malaise,impaired cognitive development, disrupted linear growth, chronic inflammation, and anemia [2].Current WHO recommendations focus on the control of STH-associated morbidity viaMDA of albendazole (ALB) or mebendazole, often donated to endemic countries by the phar-maceutical industry. Target populations include pre-school age children (PSAC), school agechildren (SAC), and women of childbearing age, including pregnant women in their secondand third trimesters. The WHO strategy for SAC recommends that MDA programs targetSAC annually where prevalence is 20%–50% and biannually where prevalence is over 50%.These programs are primarily delivered using school-based platforms with teachers serving asdrug distributors. In alignment with the WHONTD Roadmap, this sustained control strategyaims to decrease worm burden and reduce STH-associated morbidity by ensuring that 100% ofendemic countries are reaching PSAC and SAC with at least 75% coverage by 2020 [3].However, in 2013, only 39% of SAC and 49% of PSAC in need of treatment were reachedwith MDA, and only 27% of endemic countries currently attain London Declaration coveragePLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004737 July 14, 2016 1 / 4a11111OPEN ACCESSCitation: Means AR, Ásbjörnsdóttir K, MwandawiroC, Rollinson D, Jacobson J, Littlewood T, et al. (2016)Sustaining Progress towards NTD Elimination: AnOpportunity to Leverage Lymphatic FilariasisElimination Programs to Interrupt Transmission ofSoil-Transmitted Helminths. PLoS Negl Trop Dis 10(7): e0004737. doi:10.1371/journal.pntd.0004737Editor: Patrick J. Lammie, Centers for DiseaseControl and Prevention, UNITED STATESPublished: July 14, 2016Copyright: © 2016 Means et al. This is an openaccess article distributed under the terms of theCreative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.Funding: The authors received no specific fundingfor this work.Competing Interests: The authors have declaredthat no competing interests exist.targets [4]. As endemic countries aim to rapidly scale up STH programs to achieve the 2020goals, they are also faced with the challenge of sustaining programs indefinitely to continuemorbidity suppression in vulnerable populations. This is largely because most STH strategiesdo not address adult reservoirs of infection; in some cases, up to 80% of hookworm parasitesand 30% of Ascaris and Trichuris worms are harbored in adult populations [5–7]. Recent evi-dence from mathematical models suggests that in some settings, interrupting STH transmis-sion using MDAmay only be feasible if annual treatment is broadened to include adults [8].A potential strategy for broadening the reach of STH programs is to leverage the existingcommunity-based infrastructure of LF elimination programs. LF (includingWuchereria ban-crofti, Brugia malayi, and Brugia timori species) is a disease caused by mosquito-transmittedparasitic worms that damage the human lymph system, resulting, most recognizably, in lymph-edema, elephantiasis, and hydrocele. The WHO strategy for LF recommends annual MDA ofALB and either ivermectin or diethylcarbamazine (DEC) to all individuals living in endemicareas beginning at two years of age (for the ALB and DEC regimen) or five years of age (forALB and ivermectin). Following four to six annual rounds of MDA, the density of circulatingmicrofilaria in infected individuals (and thus the community-level force of infection) may bereduced and LF transmission disrupted.Over 1,000,000,000 people across 55 countries are in need of MDA for LF [9]. Despite thislarge target population, LF elimination programs have demonstrated success in interruptingdisease transmission of the infecting organism in many settings. Transmission assessment sur-veys (TAS) determine whether a given implementation unit meets specific operational andinfection criteria and can successfully stop MDA for LF and transition to post-MDA surveil-lance. To date, 46 countries have implemented a TAS to assess readiness for cessation of MDAin at least one implementation unit, and 18 national LF programs have successfully moved topost-MDA surveillance [9].There are a number of compatibilities between LF and STHs that would facilitate a coordi-nated LF surveillance and STH disease elimination strategy. First, the diseases are geographi-cally congruent; 72 countries are co-endemic for LF and STHs, and in 2014, 85% of thepopulation in need of treatment for STHs lived in LF-endemic countries [10]. Second, bothimplementation of the LF TAS and routine STH prevalence surveys require sample collectionfrom school-age populations, although sample types differ. Third, both LF and STH programsutilize MDA with ALB as chemotherapeutic interventions, and ivermectin (used in areas co-endemic for LF and onchocerciasis) also has efficacy against STH infections, including Tri-churis [11].As a result, community-based LF programs have undoubtedly already contributed to thedecline of STHs in co-endemic areas. After two rounds of LF MDA with DEC and ALB inHaiti, the prevalence of Ascaris, Trichuris, and hookworm was reduced by 24.9%, 55.3%, and82.1%, respectively. Significant reductions in infection intensity were also observed. Addition-ally, although women of reproductive age were not provided ALB during LF MDA, Trichurisinfection prevalence decreased comparably across women, children, and men, indicating thatLF MDA may have reduced the force of STH infection [12]. Similar reductions in STHs wereobserved amongst SAC in Tanzania following MDA with ivermectin and ALB for LF [13].Transitioning community LF MDA programs to STH programs that deliver treatments toPSAC, SAC, and adults may reduce residual infections harbored in non-SAC populations aswell as in SAC who are not enrolled in school, and thus be a viable approach to sustainingprogress toward interrupting STH transmission. The acceptability associated with many LFprograms would benefit STH programs as they engage with new target populations. Finally,although STH resistance to benzimidazole anthelmintics has not been confirmed in humans, ithas been observed in nematode infections of livestock [14]. One theoretical approach toPLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004737 July 14, 2016 2 / 4decreasing the risk of inducing resistance is to shorten the duration of drug pressure by broad-ening target populations and more rapidly interrupting STH transmission.For these reasons, leveraging the existing infrastructure (including the health workers, sup-ply chains, and delivery schedule) and success of LF programs may be a unique opportunity tofacilitate a smooth transition to a community-based STH platform. At the same time, LF pro-grams that have achieved post-MDA surveillance status will continue to benefit from an ongo-ing infrastructure to facilitate the surveillance activities necessary for monitoring potentialrecrudescence or collecting data for WHO elimination dossiers. There are a number of poten-tial challenges to integrating LF and STH platforms. Most notably, utilizing community-basedLF platforms to serve as the primary method to deliver STH services will require political aswell as logistical changes. Where STH programs are primarily administered by ministries ofeducation, there will need to be close coordination with ministries of health. Methodologicalinnovations will also need to accompany the proposed programmatic shift to ensure that coor-dinated sampling methodologies are validated and field deployable diagnostics are available forrelevant coordinated surveys. This presents a major challenge that will require technologiesand processes to enable the simultaneous sampling, storage, and testing of fecal and serumspecimens.The design of relevant field studies will need to account for complex issues such as randomi-zation of communities on various LF elimination trajectories and with varying access to co-interventions such as water and sanitation activities. Hybrid trials that blend efficacy and effec-tiveness (including randomized trials) and implementation research studies will be necessaryfor implementing simultaneous process evaluations that provide context for clinical findingsand inform future guidelines. Perhaps the largest undertaking on the research agenda will bedefining, testing, and validating STH transmission breakpoints. Meanwhile, ministries ofhealth will be challenged by partnering with researchers to facilitate the intensified trials inselect areas while continuing STH control policies broadly.In light of these research needs, the Bill & Melinda Gates Foundation recently launched theDeWorm3 Project in partnership with the Natural History Museum (NHM) in London. Thepurpose of DeWorm3 is to test the feasibility of interrupting transmission of STHs by leverag-ing existing LF elimination efforts. The project will require cluster randomized trials of a num-ber of intensified STH interventions, including community-wide MDA, cost-effectivenessanalyses, qualitative studies of compliance and stakeholder satisfaction, mathematical model-ing exercises, drug resistance monitoring, and a number of other research initiatives thatexplore the unique opportunity to innovatively transition from STH control to eliminationstrategies.The prospect of leveraging LF platforms to benefit STH programs in co-endemic areas hasbeen promoted since the initial establishment of the Global Alliance to Eliminate LymphaticFilariasis (GAELF) in 2000 [15]. As an increasing number of LF programs transition to post-MDA surveillance, the opportunity to leverage these valuable platforms to sustain the gainsobserved in STH co-endemic areas has never been more clear, nor more timely. This is amoment of enormous opportunity for programs, policy makers, and communities to cometogether to eliminate the public health risks associated with STH infection.References1. Anderson RM, Turner HC, Truscott JE, Hollingsworth TD, Brooker SJ. Should the Goal for the Treat-ment of Soil Transmitted Helminth (STH) Infections Be Changed fromMorbidity Control in Children toCommunity-Wide Transmission Elimination? PLoS Negl Trop Dis. 2015; 9(8):e0003897. doi: 10.1371/journal.pntd.0003897 PMID: 262915382. Hotez P. Helminth Infections: Soil-transmitted Helminth Infections and Schistosomiasis. In: DiseaseControl Priorities in Developing Countries. 2nd ed. World Bank; 2006.PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0004737 July 14, 2016 3 / 43. World Health Organization. Accelerating Work to Overcome the Global Impact of Neglected TropicalDiseases: A Roadmap for Implementation. Geneva, Switzerland; 2012.4. Country Leadership and Collaboration on Neglected Tropical Diseases, in Third progress report of theLondon Declaration, Uniting to Combat Neglected Tropical Diseases; 2015.5. Elkins DB, Haswell-Elkins M, Anderson RM. The epidemiology and control of intestinal helminths in thePulicat Lake region of Southern India. I. Study design and pre- and post-treatment observations onAscaris lumbricoides infection. Trans R Soc Trop Med Hyg. 1986; 80(5):774–92. PMID: 36036176. Bundy DA, Cooper ES, Thompson DE, Anderson RM, Didier JM. Age-related prevalence and intensityof Trichuris trichiura infection in a St. Lucian community. Trans R Soc Trop Med Hyg. 1987; 81(1):85–94. PMID: 34453307. Bradley M, Chandiwana SK, Bundy DA, Medley GF. The epidemiology and population biology of Neca-tor americanus infection in a rural community in Zimbabwe. Trans R Soc Trop Med Hyg. 1992; 86(1):73–6. PMID: 15663148. Anderson R, Truscott J, Hollingsworth TD. 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Sustaining Progress towards NTD Elimination: An Opportunity to Leverage Lymphatic Filariasis Elimination Programs to Interrupt Transmission of Soil-Transmitted Helminths.

Sustaining Progress towards NTD Elimination: An Opportunity to Leverage Lymphatic Filariasis Elimination Programs to Interrupt Transmission of Soil-Transmitted Helminths

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