Introduction
More than half of the world’s population lives in places endemic for soil-transmitted
helminths (STHs), and an estimated 1.45 billion people are infected [1,2]. In 2017,
the global burden of STH infection (Ascaris lumbricoides, hookworm, and Trichuris
trichiura) was estimated at 1.9 million disability-adjusted life years (DALYs) [3].
Moderate and heavy infection intensity and chronic STH infection are associated with
anemia, malnutrition, educational loss, and cognitive deficits, but recent systematic
reviews and meta-analyses produced conflicting results on the impact of preventive
chemotherapy (PC) [4–6].
The Soil-Transmitted Helminthiasis Advisory Committee (hereafter called “the Committee”)
is a group of independent experts with a broad range of expertise. It is convened
annually by Children Without Worms (CWW), an organization whose purpose is to utilize
available evidence to identify best practices and opportunities for the prevention
and control of STH infection [7]. On November 1 and 2, 2017, the Committee met in
Baltimore, Maryland, United States of America, in order to discuss the critical need
to develop a data-driven guide to the STH endgame on late-stage program functioning,
processes, and surveillance. The focus was on research and field experiences from
countries approaching the “elimination of STH infection as a public health problem”
after consecutive years of PC and countries that are now considering scaling down
their PC frequency but may be concerned about infection rebound. Emphasis was placed
on interim recommendations for monitoring and decision-making for national program
managers desiring to achieve the World Health Organization (WHO) goal of eliminating
STH infection as a public health problem by 2020, particularly related to STH infections
in risk groups other than school-age children (SAC), namely preschool-age children
(PSAC) and women of reproductive age (WRA) [8]. The following is the Committee’s recommendations
stemming from the Baltimore meeting in November 2017. It complements and updates the
publication derived by the Committee’s meeting a year earlier in Basel, Switzerland
[7], and was instrumental in shaping the agenda for the October 2018 meeting, convened
jointly by CWW and WHO, with recommendations to be reported elsewhere.
The 2020 roadmap and beyond
In its roadmap for implementation for 2020, WHO set a goal to achieve at least 75%
coverage of PC—either annual or biannual—of SAC and PSAC [9–11]. As we approach 2020,
it is imperative that we not only accelerate what has worked for the control of STH
infection–related morbidity but that we look beyond 2020 and better understand what
more is required to eliminate STH infection as a public health problem.
Fig 1 summarizes progress made in terms of both coverage and impact using 2016 country
data. Despite considerable gains in SAC coverage, less than half of the at-risk countries
are treating PSAC, a number that has not changed much in recent years, yielding a
total coverage level of approximately 50% but with considerable variability of coverage
from year to year and across countries (Fig 2). If the current trend in PC coverage
persists, PSAC and the combined group of children aged 1–14 years will not reach the
goal by 2020. Accelerating PSAC PC coverage might avoid that failure, and hence, needs
a clear, strong global policy now. While the initial focus on SAC coverage has enabled
the mobilization of resources, other priorities have emerged, both in places and populations
in which the target was not achieved and within areas that are now shifting priority
from scaling up PC to eliminating STH infection as a public health problem—defined
by the WHO as when less than 1% of the at-risk population has moderate or heavy infection
(MHI) [8]—and potentially interrupting the transmission of STH infection [12]. WHO
recommends stopping PC once less than 1% of the at-risk population has MHI infections.
Surveillance will, however, need to continue in order to pick up potential recurrence
of infection and to plan further intervention, if warranted. Hence, as we turn our
sights towards and beyond 2020, the Committee recognized it as timely to review and
assess the successes and challenges of progress made to date. Indeed, it is hoped
that the Baltimore 2017 meeting deliberations will inform future control strategies
and targets.
10.1371/journal.pntd.0007201.g001
Fig 1
Progress for PC coverage (by country) in SAC and where STH infection is no longer
considered a public health problem (MHI <1%).
Source: 2016 PC data from WHO. * Country with detailed epidemiologic information available.
MHI, moderate or heavy infection; PC, preventive chemotherapy; SAC, school-age children;
STH, soil-transmitted helminth.
10.1371/journal.pntd.0007201.g002
Fig 2
Global PSAC treatment and coverage, 2006–2016.
Source: WHO PC Databank, PSAC PC coverage data from 2006–2016; http://www.who.int/neglected_diseases/preventive_chemotherapy/lf/en/.
* Coverage is calculated by dividing the number of children requiring PC and treated
by the total number of children in need of PC. PC, preventive chemotherapy; PSAC,
preschool children; WHO, World Health Organization.
There have been many important developments by the time the Committee convened in
November 2017, but six are particularly noteworthy:
updated PC guidelines published by WHO for all at-risk populations [13];
the Bellagio Declaration focusing on girls and WRA [14];
widening of WHO’s engagement with experts around the globe [15];
success of the Global Program to Eliminate Lymphatic Filariasis (GPELF) [16];
increasing importance for deworming programs to measure impact [17]; and
the launch by WHO-AFRO of the Expanded Special Project on the Elimination of Neglected
Tropical Diseases (ESPEN) portal (http://espen.afro.who.int), which provides—for the
first—subnational data on disease endemicity and PC coverage for each of the five
PC-NTDs, including STH infection.
In this Policy Platform, we lay out critical challenges in seven key areas that need
attention, discuss progress until November 2017, and put forward recommendations for
immediate action. Our recommendations arose at a critical juncture for STH control
efforts, as current global policies, goals, and related strategies and resources are
revitalized through 2020, a year which is upon us.
Challenges and recommendations
Challenge #1: Incomplete and inconsistent monitoring of program impact
Recommendation: Define standard impact goals and targets post-2020
To date, programs mainly focused on reporting on PC coverage, as guided by a simplified
coverage target specified by the Roadmap; yet there are few standardized data on program
impact. It is noteworthy that country programs are increasingly interested in quantifying
the impact of deworming on health outcomes [17–19]. Current approaches to measuring
impact vary across countries and across deworming program implementers, limiting comparability
and the possibility to appreciate changes over time and across countries and regions.
Moreover, impact data are not readily available, with most of the evaluations conducted
by research groups. For the Africa region, there has been recent progress in data
sharing and transparency for neglected tropical diseases (NTDs), through the work
of ESPEN and their data portal [20]. Currently, there is availability of data on endemicity
and coverage at the subnational level for the five PC-NTDs, including STH infection,
for 47 of 49 countries in the AFRO region. This successful approach to reporting sub-national
data should be expanded to the other WHO regions where STHs are endemic.
The ESPEN portal is starting to include impact assessment data for lymphatic filariasis
and onchocerciasis and there is an opportunity to include comparable data for STH
infection. However, this will require a standardized and comprehensive monitoring
and evaluation (M&E) framework that is tied to clearly defined, quantitative goals.
For example, globally, a reported 69.5% of SAC and 50.8% of PSAC requiring PC reportedly
received PC in 2016 [21]. It is conceivable that the observed scale-up of PC targeting
STH over the past decade was a major contributor to the decline in the global burden
of STH infection [22–25]; yet the precise extent to which this coverage has reduced
prevalence, intensity, and burden of STH infection is not known. Country programs,
in particular, require a comprehensive, standardized, yet flexible approach to measure
progress toward morbidity-related goals. Such an approach would capture essential
programmatic elements, and be used by each country to map their needs, commitment,
and resources. This will generate realistic timelines and planning processes as well
as alerting WHO, partners, and donors to better assess the resource and technical
capacity needs of each program. Subnational data with standardized indicators for
anthelmintic drug availability and coverage of the target populations are critical
to track progress at the subnational level where PC program implementation may not
be uniform. Data can also be disaggregated (e.g., by district, sex, and age categories,
and any other useful determinant) to better understand the equity of program access
and delivery for the three target risk groups (i.e., PSAC, SAC, and WRA). PC needs
for refugees and migrants are also increasingly being recognized, and hence, WHO is
considering to add these populations to the at-risk groups, while some countries (especially
those in AFRO and EMRO regions) are actively engaged in estimating access, burden,
and resource issues for migrants.
Challenge #2: Reaching at-risk groups other than SAC
Recommendation: Identify new PC strategies, platforms, and reporting mechanisms
Deworming of SAC has been shown to reduce disease burden, especially reducing high-burden
infections in a cost-effective manner, but the empirical evidence from both multiyear
deworming programs and modeling studies suggest that targeting SAC alone for PC is
insufficient for sustained control and elimination of STH infection [17,26,27]. In
particular, this is the case for T. trichiura due to poor drug efficacy [28,29] and
for hookworm due to the age distribution of infection. Indeed, in many settings, adults
are at particularly high risk of hookworm infection and thus contribute substantially
to transmission [30]. These issues are in contrast to countries where school-based
deworming has been coupled with community-based programs in both experimental studies
and as part of lymphatic filariasis control programs that target entire communities
[31]. Using an exclusive school-based intervention platform potentially excludes 12.8%
SAC who are out of school, with some countries like South Sudan having 66% of their
SAC out of school [32]. With that and the availability of a pediatric mebendazole
preparation as a donation for PSAC, out-of-school children and PSAC can be immediately
prioritized to help achieve the overall children’s coverage goal. Recent progress
has been made on a more comprehensive preventive approach to include all risk groups,
as demonstrated by the Kenya “Breaking Transmission Strategy” in addition to community-wide
PC coverage through the lymphatic filariasis elimination program through USAID. Successful
PC interventions targeting SAC by most countries are generating requests for specific
guidance on the next operational phase: how to efficiently implement sentinel surveillance
and which indicators to measure in order to predict, detect, and treat widely dispersed
and persistent pockets of transmission. There is a need to consider how to scale up
approaches to reach PSAC, given the current drug availability and added cost of this
approach. Consistent with these needs is a recognized gap in our current knowledge
of disease transmission at low prevalence and persistent environmental factors that
facilitate transmission. Thus, there is a renewed need to clearly identify research
gaps and questions that would facilitate implementation in these settings.
A recent report has provided guidance and recommendations for WRA [33]. Building on
this report, WHO needs to develop implementation guidelines linked to clearly defined
targets, both for WRA and PSAC as critical populations at risk of high STH burden
[7,14]. Operational research is also needed to define platforms, partners, and recording
and reporting tools to monitor progress of control programs targeting PSAC and WRA.
In addition, there remains the challenge of providing additional anthelmintic drugs
necessary to treat WRA (not targeted by the current donations). There is optimism
that there will be the possible donation of chewable Vermox from Johnson & Johnson
(J&J) for PSAC, but the quantities donated may not be enough to cover the total numbers
at risk. Consideration of new drug options for WRA needs immediate discussion at national,
regional, and global fora. Data from the GPELF and other community-based PC programs
may provide insight into efficacy and safety issues through birth cohort studies.
Challenge #3: The risk of anthelmintic drug resistance
Recommendation: Develop standardized indicators to detect emerging resistance
Experience from the veterinary sector demonstrated that anthelmintic drug resistance
developed after years of large-scale monotherapy [34]. We suspect that if we wait
until resistance is clinically detected in humans, it will be too late to respond
[35]. While progress is being made, there are currently no routine, field-applicable
diagnostics that can effectively identify and monitor signs of emerging resistance,
so research on developing such tests urgently needs financial support. Indeed, we
need to better identify resistant genes and to track refugia (i.e., that proportion
of the worm population that remains susceptible to anthelmintic drugs). Human populations
with a long history of single-drug deworming that have low worm burdens but have not
reached transmission break points are likely to be at the greatest risk for the development
of drug-resistant parasites. For diagnostic approaches such as quantitative polymerase
chain reaction (qPCR) to be used in an STH-programmatic setting, we need to take molecular
diagnostics to a level at which we can use its full potential by standardizing analysis
and reporting and including appropriate quality control measures [36]. A standardized
approach to the monitoring of potential emerging resistance needs to be established,
especially in those countries that have mature PC programs (e.g., Mexico and Togo,
among others), to track both drug efficacy and mutations known to be associated with
resistance [37].
Challenge #4: Poor diagnostics to assess program needs by implementation stage
Recommendation: Employ validated program stage-specific diagnostic techniques
There is a need for new diagnostics that are appropriate for informing key decision
points for national STH control programs [38,39]. The Kato–Katz technique, while relatively
inexpensive, widely used, and sensitive in detecting MHI, will have lower positive
predictive values in low-prevalence (and low-intensity) settings [40,41]. In addition,
some preliminary analysis from microscopy and PCR has suggested that hookworm infection
may be misidentified. New diagnostic tests have been validated [7], yet there is a
need for novel, highly sensitive tests that can be employed in settings that move
from STH control to elimination. However, their specific role and use in the context
of national program implementation needs to be assessed [41]. Furthermore, capacity
strengthening for national programs will be needed to fully take advantage of any
new diagnostics. Field and laboratory protocols need to be standardized, reference
laboratories established, and training developed for different contexts and languages.
Gaps in the current diagnostic landscape have been identified, and formative research
is underway. The next steps are to finalize and disseminate results and to identify
additional resources for gap areas (e.g., sustaining animal models, conducting field
studies to calculate test performance in various settings, etc.). Guidelines will
then need to be developed to inform country programs on how to incorporate these tests
for improved assessment of program impact and further planning.
Challenge #5: Limited efficacy of current drugs and gaps in drug availability
Recommendation: Promote research into combination therapies and fast track pre-qualification
processes
The existing anthelmintic drugs have variable efficacies against different STH species,
with particularly low efficacies against T. trichiura when using single-dose treatments
[29]. New efforts must be undertaken to identify and provide guidelines for use cases
for combination therapies in general and specifically in which T. trichiura is the
predominant species [42]. In 2018, the WHO Essential Medicines Committee approved
the inclusion of ivermectin for both STH and Strongyloides stercoralis to the WHO
Model List of Essential Medicines [43]. However, there are implications and potential
challenges in adding ivermectin to albendazole and mebendazole in STH deworming programs.
Merck provides ivermectin dedicated for the control of lymphatic filariasis and onchocerciasis,
and new manufacturers will need to become prequalified to meet the growing demand
from STH control programs. Additionally, bioequivalence studies and other considerations
will be needed to make the drug available at low cost. This will take time and requires
innovative financing mechanisms.
Challenge #6: Limited coordination with the water, sanitation, and hygiene (WASH)
sector
Recommendation: Identify WASH indicator(s) to be included in routine STH M&E
As articulated in an editorial put forth in The Lancet [44], the 2020 WHO roadmap
identified the critical role of WASH in the control of STH infection but did not set
actionable targets or strategies [11]. The STH community has largely avoided establishing
an approach for addressing WASH or establishing a structure for engagement with the
WASH sector. However, the recent development of the WASH–NTD joint strategy provides
an entry point and guidance for improved communication, coordination, and collaboration
[45]. Ample observational evidence [46,47], some recent randomized trials, biological
plausibility, and history suggest that improved WASH is critical in the control and
elimination of STH infection. Alignment with the WASH sector, specifically including
WASH indicators as part of STH M&E [48] (and vice versa) by using data to advocate
for WASH activities in STH-endemic areas, employing program monitoring, and conducting
operational research and advocacy to ensure normative inclusion of STH-related WASH
behaviors (e.g., shoe-wearing [49]), would be valuable contributions in STH control
programming. Better quantification of the specific mechanisms and use of consistent
indicators across programs would provide support to the WASH sector on gaps in typical
WASH programming (e.g., type of water sources or food hygiene).
Challenge #7: New targets needed for post-2020
Recommendation: Develop clearly defined, quantitative program targets for all at-risk
groups and move beyond PC coverage estimates
One of the most important next steps as we move toward 2020 and beyond is the need
to establish clearly defined, quantitative program goals and targets post-2020. The
current targets of achieving at least 75% coverage for deworming for SAC (and PSAC)
is in reach, but we know that even meeting this target is insufficient to achieve
elimination of STH as a public health problem. We must also critically evaluate whether
the threshold of 1% prevalence of MHI is useful for M&E of STH morbidity control and
moving toward elimination. There is a need to look beyond simple PC coverage measures
and include impact targets for PSAC and WRA, benchmarks for WASH that will encourage
investment in WASH in STH-endemic areas, and estimates of PC uptake along the distribution
chain that would give accurate estimates for not only availability of the drug, but
population compliance. Addressing Challenges 1–6, articulated above, will support
this critical effort.
Outlook
There has been substantial progress in increasing coverage of PC for the control of
STH infection, particularly among SAC and, to a lesser extent, among PSAC. As we approach
2020, work remains to accelerate action to achieve these targets in many places. At
the same time, we need to think critically about what is needed beyond the 2020 roadmap
and increase efforts in the seven areas discussed in this Policy Platform. This needs
to be achieved through active collaboration and coordination by pertinent government
ministries, researchers, donors, WHO, drug manufacturers, and multisectoral collaboration
[50]. In doing so, it will help ensure progress toward eliminating STH infection—and
other NTDs—as a public health problem, and it will yield more efficient allocation
of resources and greater sustained impact, driven by targets and thresholds based
on scientific evidence.