Professional Documents
Culture Documents
3
4
Review
Latest WHO Global burden* WHO Roadmap targets Partnerships and alliances Endemic Treatment progress Research and operational
resolutions, countries needs
year
DALYS (millions) Deaths per year 2015/2017 2020
(Continued from previous page)
Echino- .. 0·14 1200 Pilot projects to Validated strategy .. .. Limited data available, but no change in Implement pilot strategy in
coccosis validate effective available for global distribution since 2010; high areas of high risk
strategies where echinococcosis/ prevalence (5–10%) of cystic disease in
disease is a public hydatidosis and parts of Latin America, China, Central
health problem (eg, interventions scaled up Asia, and Africa; alveolar disease has high
major burden in in selected countries for prevalence in Tibetan Plateau with
China) their control and incidence of 16 000 cases; cross-sector
elimination coordination with authorities to
implement known control measures —
carcass condemnation; deworming of
dogs and reduction of access to offal;
introduction of diagnostic ultrasound;
and promotion of PAIR (puncture,
aspiration, injection and respiration)
surgery strategy
Foodborne .. 1·88 7000 deaths .. 75% of population at .. 17 Reduced numbers of cases reported in Define extent of endemic
trematodes reported in 2005 risk of infection reached Egypt of fascioliasis; increased areas; develop serological and
but not by GBD by preventive treatments for fascioliasis in Peru and molecular methods for
study; 7·9 million chemotherapy; Bolivia since 2009; increased improved diagnosis; increase
cases with severe morbidity controlled in treatment programme for access to praziquantel (or
sequelae all endemic countries opisthorchiasis in Laos and in Vietnam triclabendazole for
for clonorchis; mapping of areas of fascioliasis); engage with
endemicity in Cambodia and initiation other sectors to reduce risk via
of treatment programme health education and
improved sanitation
Lymphatic WHA50.29, 2·78 .. By 2017, 70% of all 81 100% of all endemic Global Alliance to Eliminate In 2014, Continued maintenance of Implement albendazole
filariasis 1997 endemic countries will countries will have been Lymphatic Filariasis (GAELF) 73 treatments—peak of 559 million 2 times per year in Loa loa
have met the criteria verified as free of countries achieved in 2014; 11 countries have co-endemic areas with vector
to stop interventions transmission or will not commenced MDA programmes; control via impregnated
and entered the post- have entered post- 23 countries have implemented bednets; scale-up
intervention intervention limited MDA but not reached 100% interventions in newly defined
surveillance phase surveillance geographical coverage—insufficient to endemic areas; assess impact
reach 2020 target of elimination; of onchocerciasis programmes
18 countries moved into surveillance on filariasis endemicity and
phase following Transmission impact of lymphatic filariasis
Assessment Surveys; programmes on soil-
diethylcarbamazine available as transmitted helminthiases;
donated product since 2013–14 develop a short duration
macrofilaricide based on anti-
wolbachia antibiotics as a
substitute for doxycycline;
complete triple therapy trials;
increase efforts to address
morbidity
(Table continues on next page)
5
6
Review
Latest WHO Global burden* WHO Roadmap targets Partnerships and alliances Endemic Treatment progress Research and operational
resolutions, countries needs
year
DALYS (millions) Deaths per year 2015/2017 2020
(Continued from previous page)
Bacteria
Buruli ulcer WHA57.1, 5000–6000 Oral antibiotic therapy 70% of cases detected Global Buruli Ulcer Initiative 33 12/15 countries that report regularly Rapid point of care diagnostic
2004 cases per year incorporated into early and cured with reported 2200 new cases in 2014
control and treatment antibiotics in all compared with 5000 in 2009
endemic countries
Leprosy WHA44.9, 0·006 No deaths .. Global elimination of International Leprosy .. See text Focus on countries with
1991 attributed the public health Elimination Programme continuing high prevalence
problem
Trachoma WHA62.1, 0·33 No deaths 10% of endemic All countries will have International Trachoma .. Global Trachoma mapping Project Implement expanded
(avoidable 2009 attributed countries were achieved the UIG and be Initiative and GET 2020 completed enabling scale up of SAFE trichiasis surgery
blindness) expected to have free from blinding strategy; Number of individuals
achieved the UIG by trachoma as a public- receiving azithromycin increased from
2013; by 2016, 40% health problem 45 million in 2010 to 54·7 million in
of endemic countries 2014, with increased number of districts
achieved this goal and treated; trichiasis surgery delivered in
entered post-endemic 43% of districts where it was defined as a
surveillance public health problem with target to
exceed 50% by 2015
Yaws/ WHA2.6, Not calculated .. .. Global eradication .. .. Pilot studies show success of ..
endemic 1949 azithromycin treatment strategy
trepone-
matoses
Non-infectious NTDs
Snake bite .. .. 96 000 per year .. .. Global Snake Bite Initiative .. Production of antivenom stopped by Develop polyvalent
manufacturers and no quality antivenom not needing cold
alternatives available for common chain; advocate for greater
snakebite in Africa attention to snake bite as
cause of mortality
Podo- .. .. No deaths .. .. International Podoconiosis .. Increased recognition of problem over Implement morbidity
coniosis attributed Initiative (Footwork) recent years; definition of areas of management
endemicity
Data are derived from various sources.6,8,46,52,53,57 MDA=mass drug administration. UIG=ultimate intervention goal. *Global Burden of Diseases, Injuries, and Risk Factors Study 2010 data.
Table: Neglected tropical diseases and the associated global burden, targets, partnerships, endemic countries, treatment progress, and research needs
Science underpinning the NTD case and anxiety of patients with NTDs as well as caregivers
The burden of NTDs has only recently been highlighted as a problem with
The Global Burden of Disease study of 201017 attributed significant additional burden.20
some 27 million disability-adjusted life years (DALYs) to
NTDs. A 2014 study18 included other conditions not Definition of research priorities
included within the WHO official NTD list of 17 diseases, Research priorities for NTDs have been published in a
and attributed 47·9 million DALYs to all NTDs; another series of reports by WHO and the Special Programme
study5 in 2009 estimated the burden for NTDs was for Research and Training in Tropical Diseases, outlining
56 million DALYs. The global annual mortality from priorities for kinetoplastid parasites (trypanosomes and
NTDs was reported as around 150 000 deaths per year by leishmanias), helminth infections, zoonoses and viral
the Global Burden of Disease study.17 However, this infections (dengue, and other arboviruses).26 A consensus
estimate excluded deaths from rabies (55 000 deaths), has been reached that new drugs, insecticides, and
snakebite (up to 94 000 deaths), cancers associated with diagnostics are required, which will offer improved and
trematode infections (60 000 deaths), and neurological cost-effective therapies, vector-control tools, and
NTD conditions such as neurocysticercosis-related diagnostics. Attempts to develop vaccines for multi-
epilepsy (60 000 deaths)—these deaths are also included cellular parasites are yet to develop a product for large-
in other categories. These figures suggest the total scale use. However, progress to address the expanding
annual mortality from NTDs is actually around 350 000. dengue threat has been made with the development of a
In 2010, WHO reported that schistosomiasis mortality vaccine for dengue (Dengvaxia, Sanofi Pasteur, Lyon,
alone could be as high as 280 000 per year in Africa—a France). Dengvaxia has been licenced in Mexico for use
20-fold difference from the official GBD data.19 Morbidity in highly endemic areas, after results of safety and
from permanent blindness, debilitating skin disease, efficacy studies in clinical trials showed reduced
disability and disfigurement with long term psychological incidence of hospitalisation in vaccinated children
and social and economic consequences will elevate the aged 2–16 years old in three clinical trials involving
total DALY burden but are not included in Global Burden 35 000 children.27
of Disease metrics.20 Research to improve delivery of existing products and
evaluate efficacy of existing therapeutics will be necessary,
NTD comorbidities: HIV, epilepsy, and cancer as will exploration of combinations of products known to
A possible association between HIV and urogenital be effective. Specific research priorities are improved oral
schistosomiasis has been recognised. Ndeffo Mbah and therapy for human African trypanosomiasis that is
colleagues21 showed increased HIV positivity in females effective in both early and late stage disease; and
infected with Schistosoma haematobium. The opportunity improved chemotherapy for leishmaniases, Chagas’
to reduce the risk of HIV in young females (5–15 years) disease, and buruli ulcer—current therapies are not ideal
associated with S haematobium urogenital pathology by owing to the duration of required treatment, mode of
annual praziquantel has yet to be recognised by the HIV administration, and toxicity. A short-duration macro-
community, despite the need to achieve high coverage of filaricidal treatment to kill or permanently sterilise adult
this at-risk group irrespective of a direct link to HIV. The filarial worms is still needed, because despite the efficacy
safety of praziquantel has been reconfirmed during of the anti-Wolbachia antibiotic, doxycycline, the duration
pregnancy and lactation.22 The longstanding policy to of treatment and eligibility criteria currently restrict its
assure coverage of young females with praziquantel widespread use. Praziquantel has been donated for mass
treatment should be implemented by both the NTD and drug administration in school-aged children for
HIV constituencies. Neurocysticercosis infection caused schistosomiasis; however, it needs to be reformulated for
by Taenia solium cysts has been associated with epilepsy paediatric use given that pre-school children are
and estimates suggest some 30% of global epilepsy is frequently infected. The combination of praziquantel
associated with neurocysticercosis.23 Bladder cancer with artesunate for treatment of both adults and juvenile
associated with S haematobium and food-borne trematode forms of schistosomes might be considered.28
infections that cause cholioangiocarcinoma are estimated Research linked to implementation of programmes and
to cause 60 000 deaths annually.24 The successful challenges that programmes face as they mature require
schistosomiasis control programme in Egypt has seen a social science involvement to improve coverage and
rapid decline in bladder cancer during the past adherence, and improved methodologies to evaluate
2 decades.25 Comorbidities associated with hookworm impact and address problems identified in acceptability
and schistosomiasis also exacerbate malaria pathology, adherence and coverage.29 Research to understand
particularly in pregnancy, which reduces birthweight and interactions between social networks within communities
increases risk of neonatal and infant mortality. Further, could help ensure optimum understanding and uptake of
the mental health comorbidity of many NTDs and the drugs.30 Increasingly complex and diverse research
impact these conditions have on the psycho-social status questions have emerged as programmes dependent on
of individuals and families, particularly depressive illness mass drug administration have progressed. Such questions
relate to the duration and frequency of mass drug in Africa; albendazole twice a year for lymphatic
administration for different diseases, the broad spectrum filariasis in L loa co-endemic areas; bednet coverage to
effectiveness of the anthelminthics used and the impact of eliminate lymphatic filariasis; and the use of doxycycline
vector control on transmission of filariasis.31 as a macrofilaricide or ivermectin four times per year in
some areas of onchocerciasis endemicity, such as in
Mapping disease distribution Brazil and Venezuela.31,38 Thomsen and colleagues39
Accurate mapping of disease distribution is a prerequisite examined a triple combination of diethylcarbamazine,
for effective implementation. Onchocerciasis pro- albendazole, and ivermectin for filariasis and showed
grammes have shown the importance of defining that microfilaria levels remain suppressed for a
endemicity; in these programmes, levels of endemicity 24 month period thus providing an opportunity to
were defined by rapid epidemiological assessment and reduce the frequency of mass drug administration in
mapping.32 The serious adverse events associated with areas where onchocerciasis is not co-endemic.
Loa loa co-endemicity with onchocerciasis meant a rapid Additionally, to reduce the problem of the limited effect
mapping methodology was required to define areas of of albendazole on trichuris infections, ivermectin
highest risk.33 Similar rapid mapping using antigen should be considered; however, ivermectin is not
detection methods are used to identify where lymphatic donated for trichuris infections or for scabies. Because
filariasis mass drug administration should be instituted.34 extensive insecticide resistance exists in Africa, the
The need to know the distribution of NTDs that can be value of bednets to eliminate Wuchereria bancrofti
controlled or eliminated by preventive chemotherapy led transmission needs to be reassessed.40
to the development of online resources to ensure all
requisite data are available and updated. The Global Cochrane systematic reviews: the deworming debate
Trachoma Mapping Project is an example of how mobile In 2015, the Cochrane Collaboration challenged the
phone and geographic information system technologies benefits of deworming for the control of soil-transmitted
can be used: population-based prevalence surveys are helminthiases after their analysis41 of randomised
done in all districts where trachoma is suspected to controlled trials (RCTs). This finding provoked robust
acquire data on burden and risk, thus enabling debate42 about whether RCTs are an appropriate way to
prioritisation of interventions and policy determination measure the nutritional and educational benefits of
for implementation of the surgery, antibiotics, facial preventive anthelminthic chemotherapy. Most RCTs do
cleanliness, and environmental improvement (SAFE) not take into account that recovery from nutritional
strategy.35 Detailed mapping of foci of human African deficits is a process that takes much longer than 1 year,
trypanosomiasis due to Trypanasoma brucei gambiense especially if the quality and quantity of the nutrients
infection has defined areas of highest risk for active assumed in the diet are limited.
surveillance.36 Furthermore, a significant proportion of individuals
Use of remote sensing technologies to produce datasets treated with preventive chemotherapy are uninfected but
that precisely define zones of climate (rainfall indices, cloud are nevertheless treated for logistical reasons and thus no
cover), physical parameters (altitude, soil type), and nutritional benefits are expected to accrue in this group.
ecological parameters (forest cover, vegetation type) is RCTs normally calculate the mean benefit of preventive
increasingly important, as predictors of disease ecology chemotherapy on the entire treated group but the true
reflecting drivers of transmission of vector borne infections. benefits are obtained only by those infected and are
Definable physical characteristics such as soil type are therefore greatly diluted.
For the NTD global mapping tool associated with podoconiosis distribution.37 The NTD global Additionally, different worm species have different
see http://www.NTDMap.org) mapping tool provides an interactive means to assist the pathological effects—hookworm causes anaemia,
planning and implementation of preventive chemotherapy ascariasis retards growth43—hence when the results of
for NTDs, enabling visualisation of geographical preventive chemotherapy are evaluated it is important
distribution of diseases and the priority areas requiring to recognise which species of soil-transmitted
mass drug administration where co-implementation should helminthiases are removed. For example, an
be initiated. The global mapping tool also complements the improvement in haemoglobin levels should not be
For the Global Atlas of Global Atlas of Helminth Infections, provides information expected if hookworms are not the prevalent species in
Helminth Infections see http:// on water and sanitation, and allows progress of interventions the population treated. On the basis of the evidence
www.thiswormyworld.org
to be tracked. from all studies including RCTs, WHO issued a
consensus statement reiterating the justification of the
The need for alternative strategies— the operational present policy of preventive chemotherapy.42 Provision
research agenda of deworming to infected populations reflects equity
Some preventive chemotherapy programmes require and ethical aspects and the intervention is recognised to
alternative strategies to reach elimination targets, which reinforce the trust in the health and education
need to be piloted and implemented. These alternative service, aspects that the Cochrane systematic review of
strategies include: ivermectin twice a year for filariasis RCTs is unable to evaluate.
Progress towards Roadmap goals 4 million since 2000. The prevalence of leprosy has
Progress on specific diseases dropped by 90%: from 21·1 per 10 000 people in 1983 to
Substantial progress towards WHO Roadmap goals and less than 0·24 per 10 000 people in 2014. A substantial
regional targets has been achieved since 2010 (table). The decrease in the global disease burden has been achieved;
Uniting to Combat NTDs initiative tracks progress on the number of leprosy cases has reduced from For Uniting to Combat NTDs
ten NTDs towards the agreed targets against a scorecard 5·2 million in 1985, to 180 618 cases at the end of 2013, see http://unitingtocombat
ntds.org
that is published annually. which has led to the suggestion that the public health
problem has been eliminated—defined by WHO as a
Dracunculiasis (Guinea worm disease) prevalence of less than 1 case per 10 000. However,
Since the introduction of the Guinea Worm Eradication although the problem of leprosy has been reduced by
Programme in 1986, 16 countries have been certified free multidrug therapy, pockets of high endemicity remain
of Guinea Worm transmission, including 6 countries in several countries, including India, Brazil, and
since 2010 (Burkina Faso, Côte d’Ivoire, Ghana, Niger, Indonesia, therefore this ancient and stigmatising
Nigeria, and Togo). However, four countries remain disease should remain a priority.49
endemic—Chad, Ethiopia, Mali, and South Sudan—who
reported only 22 cases in 2015 compared with 126 cases in Lymphatic filariasis
2014.44 Each of these endemic countries pose different In 2014, 73 countries remained endemic for lymphatic
challenges if transmission cessation is to be confirmed. A filariasis; 18 countries are now entering the surveillance
possible cycle of transmission that involves dogs, fish, and phase but 11 countries have not yet commenced mass
amphibians as paratenic hosts was discovered in Chad, drug administration programmes. Some 23 countries
meaning a change in approach could be required because have only implemented limited mass drug administration
503 dog infections were recorded in Chad in 2015; from and have not reached 100% geographical coverage.
January, to June, 2016, 498 dogs have been reported Countries that have not achieved complete coverage will
infected and four human cases have been identified in not be able to reach the 2020 target of elimination.
Chad. Human cases were also reported in South Sudan However, 18 countries have moved into a surveillance
and Ethiopia in June, 2016.44,45 In Mali, access to endemic phase following transmission assessment surveys, an
areas is curtailed due to insecurity. In South Sudan, strong evaluation which suggests transmission has been
progress has been made to reduce the numbers of infected arrested.50 However, The Gambia appears to have
villages but problems of access, population movement, eliminated transmission, without the introduction of
cattle camps, and insecurity pose end-game challenges. mass drug administration, with long-term use of
impregnated bednets for malaria control.51 A 2014
Human trypanosomiases estimate of the impact of mass drug administration
Achievement of the target to reduce the number of during the past 13 years suggests more than 96·71 million
chronic human African trypansomiasis cases to cases of lymphatic filariasis were prevented or cured; yet
between 2000–3000 cases per year by 2015 is close: 36 million cases of hydrocoele and lymphoedema
WHO reported 3796 cases in 2014 and less than 3000 in remain.52 The economic benefits estimated to have
2015. This figure was the lowest reported incidence for accrued during the first 8 years of the programme exceed
75 years and was achieved by active surveillance of $24 billion. In 2014, 559 million people were treated for
defined high-risk foci and donation of products for lymphatic filariasis and the cumulative number of
chronic human African trypansomiasis therapy treatments reported was 5·62 billion to more than
(pentamidine and nifurtimox–eflornithine).46 The 1 billion individuals.53
availability of tiny insecticide impregnated targets for The filariasis test strip, which is based on the immune-
glossina control,47 new diagnostic tests, and the prospect chromatographic test, has been introduced as an
of an oral therapy to treat both phases of the disease— improved method for use in mapping and evaluation.53
fexnidazole, which is now in phase 2 and 3 trials calls This test will be used for transmission assessment
for optimism. surveys to determine the impact of mass drug
Chemotherapy for Chagas’ disease remains administration and allow for decision making with
problematic; less than 1% of patients have access to regard to cessation or to evaluate any recrudescence.
benznidazole. Despite an impact on parasite serological Lymphatic filariasis accounts for at least 2·8 million
parameters, a randomised trial of benznidazole did not disability-adjusted life-years;17 this figure does not include
significantly reduce levels of cardiac clinical deterioration the substantial comorbidity of mental illness commonly
through 5 years of follow-up.48 experienced by patients and their caregivers.20 For WHO’s
Global Programme to Eliminate Lymphatic Filariasis to
Leprosy succeed, 100% geographical coverage of both mass drug
215 656 new cases of leprosy were reported in 2013 in administration and patient care is necessary and could be
103 countries. During the past 20 years, more than achieved through the implementation of morbidity
14 million patients have been cured of the disease, management and surgery.50
significant challenge notwithstanding the estimated generalisations about approaches to their control is
backlog of 5 million cases of trichiasis surgery; Solomon63 difficult. However, progress has been made to define
has emphasised the benefit of improved trichiasis strategies for control of specific diseases, which require an
surgery technique in reducing recurrence of trachoma. approach that goes beyond the health sector.71 The vision
for One Health is a culture change that recognises the
Yaws importance of the link between humans, animals, and
Yaws (Treponema pallidum pertenue) is a disabling skin ecosystems, providing added value by translation of the
condition that has been identified as a potential eradication One Health approach into zoonotic disease control.
target on the basis of oral azithromycin efficacy. WHO Successful application of One Health strategies are the use
developed the Morges Strategy for Yaws Eradication by of dog vaccination in the control of human rabies in Latin
2020;64 the strategy will involve mass drug administration America, KwaZulu-Natal, the Philippines, and Bali,72 and
of single dose azithromycin to entire endemic the control of the acute form of human sleeping sickness,
communities, supported by surveillance until clinical Trypansoma brucei rhodesiense, in south east Uganda. In
cases are no longer detected, and by treatment of all active Uganda,67 chemotherapy of the cattle reservoir, together
cases and their contacts. Pilot interventions have been with vector control by spraying of cattle to selectively kill
initiated in several countries: in Nsukka, Nigeria, mass the tsetse fly Glossina fuscipes, has been shown to effectively
drug administration with oral azithromycin interrupted reduce the incidence of sleeping sickness cases.67 The One
transmission within 6–12 months. In India, after a 20 year Health approach can also be applied to the control of
campaign using penicillin injection followed by sero- cysticercosis and echinococcosis, globally distributed
surveillance of children for treponemal antibodies, WHO cestode infections, in which interventions focused on
reported65 that yaws was no longer present in India and animal reservoirs (pigs and dogs) are essential components
declared its eradication (technically elimination). of interventions to reduce human prevalence allied to
behaviour change and curative therapy.73,74
Implementation strategies requiring
collaboration with other sectors Water, sanitation, and hygiene
Vector control Sustained control and elimination of soil-transmitted
Vector control has been a major component of NTD helminthiases and schistosomiasis, require not only
programmes over many decades. Many NTDs such as chemotherapy, but also access to clean and safe water
lymphatic filariasis, visceral leishmaniasis, oncho- together with appropriate waste disposal and behaviour
cerciasis, and Chagas’ disease have benefited from vector changes to reduce transmission. However, provision of
control.66 Additionally, new approaches to the control of clean and safe water in the more remote areas where
human African sleeping sickness using tiny target NTDs and other waterborne infections are most prevalent
technology47 or selective spraying of cattle to control the poses a substantial challenge and the involvement of
acute zoonotic form of disease have been shown to be other sectors is required. Engagement of the water,
effective interventions but require implementation at sanitation, and hygiene sector and the inclusion of NTDs
scale.67 Development of novel tools and methods to curb within this framework, reflects a holistic policy approach
the spread of (day-biting and outdoor-biting) Aedes aegypti within the SDG goals.62
mosquitoes that transmit dengue68 and Chikungunya69 is a
high priority, reinforced by the emergence of Zika virus. Place of NTDs in the global health context
Development of novel vector control methods will require towards 2030
substantially increased investment if they are to be During the past decade, NTDs have attracted increased
implemented.6 Increasing levels of resistance to present attention and investment. Availability of drugs is no
pyrethoid-based insecticides threaten the progress of the longer a barrier to achievement of universal health
lymphatic filariasis elimination programme in Africa.40 coverage for most NTDs yet they remain a chronic
Global warming, climate change, unplanned urbanisation, pandemic in the poorest sectors of society in endemic
and global travel of people and goods, will have an impact countries who now have access to donated drugs. Further
beyond the traditional populations associated with NTDs. progress will be driven by commitment of countries to
The establishment of schistosomiasis in Corsica contribute to the relatively small costs of delivery—
exemplifies these threats; snail populations have been estimated at 1–3% of national health budgets—to ensure
found in Corsica that are susceptible to infection with a access to donated products with a calculated annual value
parasite strain from Africa, a hybrid of S haematobium and of $2–3 billion. In 2015, 1·1 billion people received
Schistosoma bovis, therefore these strains could become preventive chemotherapy, representing a public health
established in southern Europe.70 success, and 140 million children were dewormed in a
single day in February, 2016, in India.75 However, progress
Neglected zoonotic diseases: the One Health concept towards achievement of the 2020 WHO Roadmap targets
Neglected zoonotic diseases occur in many settings, has been patchy. The resources allocated to NTDs are not
caused by diverse groups of organisms, hence yet adequate to address the totality of the problem. The
17 Murray CJ, Vos T, Lozano R, Naghavi M, et al. Disability-adjusted 40 Hemingway J, Ranson J, Magill A, et al. Averting a malaria disaster:
life years (DALYs) for 291 diseases and injuries in 21 regions, will insecticide resistance derail malaria control? Lancet 2016;
1990–2010: a systematic analysis for the global burden of disease 387: 1785–88.
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18 Hotez PJ, Alvarado M, Basáñez M-G, et al. The Global Burden of Garner P. Deworming drugs for soil-transmitted intestinal worms
Disease study 2010: interpretation and implications for the in children: effects on nutritional indicators, haemoglobin, and
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pregnancy: a phase 2, randomised, double-blind, placebo-controlled worm_wrapup_english.html (accessed July 27, 2016).
trial. Lancet Infect Dis 2016; 16: 199–208. 45 Eberhard ML, Ruiz-Tiben E, Hopkins DR, et al. The peculiar
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