WHO Roadmap Research Articles

Schistosomiasis: Snail-vector control, molecular modelling and dynamic studies of bioactive N-acetylglycoside saponins from Tetrapleura tetraptera

Schistosomiasis, a chronic neglected tropical disease caused by the Schistosoma spp. parasite, is associated with disabling patient symptoms. The new focus of the WHO roadmap on 'transmission control, wherever possible’ offers drug development opportunities for intermediate-host control to prevent human-to-snail-to-human parasite transmission. Reports on the analysis of the impact of ‘chemical-based mollusciciding’ have concluded that constant application of molluscicides may contribute significantly towards the elimination of schistosomiasis in endemic areas. In South-Western Nigeria, Tetrapleura tetraptera is a tree whose fruit has been widely used in snail vector control. The presence of molluscicidal N-acetyl triterpene glycosides in the fruit has been reported. In this study, a bioactivity-directed fractionation of the fruit extract was performed to isolate the most potent molluscicidal saponin from the fruit. In an attempt to provide mechanistic insight into the observed activity, in silico screening was performed, profiling the molluscicidal N-acetyl triterpene glycosides reported from the fruit against two potential therapeutic targets in the mollusk used, NADH-ubiquinone oxidoreductase (NAD1) and retinoid X receptor. The docking predicted binary complexes of the saponins, which were subjected to explicit solvent conformational sampling from which patterns of structural stability were obtained. The binding energies alone did not account for the potency of the saponins indicating the influence of other factor like pharmacokinetic parameters. The study concluded that there is a preferential suitability of ND1’s MWFE site for the rational design and development of novel molluscicidal agents.

Prevalence of abdominal cystic echinococcosis in rural Bulgaria, Romania, and Turkey: a cross-sectional, ultrasound-based, population study from the HERACLES project

Cystic echinococcosis is a neglected zoonotic infection that is distributed worldwide and prioritised by WHO for control efforts. The burden of human cystic echinococcosis is poorly understood in most endemic regions, including eastern Europe. We aimed to estimate the prevalence of abdominal cystic echinococcosis in rural areas of Bulgaria, Romania, and Turkey. We did a cross-sectional ultrasound-based survey that recruited volunteers from 50 villages in rural areas of Bulgaria, Romania, and Turkey. These villages were in provinces with annual hospital incidence of cystic echinococcosis within the mid-range for the respective countries. All people who attended a session were allowed to participate if they agreed to be screened. Abdominal ultrasound screening sessions were hosted in public community structures such as community halls, primary health-care centres, schools, and mosques. Lesions were classified using an adapted WHO classification. We reported the prevalence of abdominal cystic echinococcosis adjusted by sex and age through direct standardisation, using the country's rural population as a reference. From July 1, 2014, to Aug 3, 2015, 24 693 individuals presented to screening sessions and 24 687 underwent ultrasound screening. We excluded a further six indivduals due to missing data, leaving 24 681 people in our analysis. Abdominal cystic echinococcosis was detected in 31 of 8602 people screened in Bulgaria, 35 of 7461 screened in Romania, and 53 of 8618 screened in Turkey. The age and sex adjusted prevalence of abdominal cystic echinococcosis was 0·41% (95% CI 0·29-0·58) in Bulgaria, 0·41% (0·26-0·65) in Romania, and 0·59% (0·19-1·85) in Turkey. Active cysts were found in people of all ages, including children, and in all investigated provinces. Our results provide population-based estimates of the prevalence of abdominal cystic echinococcosis. These findings should be useful to support the planning of cost-effective interventions, supporting the WHO roadmap for cystic echinococcosis control. European Union Seventh Framework Programme.

What Is Next for NTDs in the Era of the Sustainable Development Goals?

In a previous article, we outlined the efforts of the Neglected Tropical Diseases (NTD) lobby to overcome the diseases' snub in the 2000 Millennium Development Goals (MDGs) and to campaign for inclusion in the post-2015 development agenda [1]. In doing so, we noted the extraordinary achievements made by the lobby despite its view from outside of the MDG juggernaut, which singled out just three for special consideration (HIV/AIDS, Malaria, and, latterly, Tuberculosis), leaving a group of previously disparate to be formulated within a plan for inclusion. The plan resulted in a three-pronged attack forged on advocacy, policy, and science. The NTD lobby has grown significantly since the original 2003 WHO/Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ) meetings were convened to float the idea that the NTDs should be reconceptualised and tackled as a group moving forward. The original core group—Peter J. Hotez, David Molyneux, and Alan Fenwick (along with WHO’s Lorenzo Savioli and others)—has since been joined by representation from academia (e.g., PLOS Neglected Tropical Diseases), the third sector (e.g., the Global Network, the Neglected Tropical Disease Non-Governmental Development Organization Network), the pharmaceutical industry, donor agencies, and the philanthropic sector (cf. Uniting to Combat NTDs). The lobby is also formally supported by the World Health Organisation (through the WHO Roadmap [2] and WHA Resolution 66.12 [3]) and by the disease endemic country governments that have signed the Addis Ababa NTD Commitment. Yet, despite boasting swelling ranks and a number of sizeable achievements in the intervening period—for instance the landmark London Declaration—the NTD lobby has remained interested in the more mainstream development agenda. The advocacy goal has always been the formal inclusion of NTDs in the successor framework to the Millennium Development Goals: the post-2015 Sustainable Development Agenda. On 1 January 2016, the Sustainable Development Goals (SDGs or Global Goals) came into force. The particulars of the goals were finalised at the United Nations summit in September 2015, and, as hoped, NTDs gained a special mention in goal 3.3: By 2030, end the epidemics of AIDS, tuberculosis, malaria, and neglected tropical and combat hepatitis, waterborne diseases, and other communicable diseases (p 16) [4]. But what is this mention worth and what are its implications? The SDGs are similar to the MDGs in that they represent time-bound targets and retain a focus on ending world poverty, but they break with the original eight MDGs in terms of their colossal scope. Composed of 17 goals and 169 targets, the SDGs are the result of an extensive three-year consultation involving multiple perspectives from government, civil society, expert groups, the private sector, and individuals. The MDGs were regularly critiqued as restricted in focus and top-down, something which cannot be levelled against the SDGs. But might the warning of the High-Level Panel that originally drafted the framework document have been ignored—The international community will need to ensure that a single, sustainable framework agenda is not overloaded with too many priorities. A product of compromise rather than decisions…? (p 14) [5]. The post-2015 vision—as articulated through the SDGs—is to create a single universal agenda in which the social, economic, and environmental dimensions of sustainability are integrated. Whereas the MDGs were criticised for targeting the low-hanging fruit, the post-2015 agenda is underpinned by the tenet “leave no one behind.” As the UN summit drew closer in 2015, we noted how this principle, coupled with the post-2015 focus on environmental issues, provided a number of advocacy issues behind which the NTD lobby began to position itself: equity, poverty, water sanitation and hygiene (WASH), climate change, quality education, NTD-related disability, and nutrition. In this paper, we reflect on the NTD lobby’s efforts to gain traction in the wide-ranging post-2015 agenda by making the case that NTDs are crosscutting and by lobbying for NTD indicators.

Integration of water, sanitation and hygiene for the control of neglected tropical diseases: a review of progress and the way forward.

A WHO roadmap to control, eliminate and eradicate neglected tropical diseases (NTDs) proposes a public health approach integrating diverse prevention and treatment interventions. Water, sanitation and hygiene (WASH) has long been a recognized, yet under-prioritized intervention of global disease control efforts. Through collaboration with the WASH sector, efforts have been made to integrate WASH in NTD control. This article reviews progress made in recent years, explores mechanisms supporting advances, and identifies priorities and next steps for accelerating WASH integration. This paper reveals advances in collaboration between WASH and NTD sectors, resulting in progress made across areas of programming; research; advocacy and policy; training and capacity building; and mapping, data collection and monitoring. Face to face meetings between WASH and NTD sector experts with a clear purpose of informing wider sector discussions, and the development of actionable joint workplans, have been particularly critical in supporting progress. Priority next steps include building capacity for WASH programming among NTD control teams, coordination at the country level, and strengthening the epidemiological evidence and operational learning for joint WASH and NTD interventions. In order to accelerate WASH integration in NTD control through strong collaborations with the WASH sector, the NTD sector could make use of strong data management skills and advocacy opportunities.

Baseline prevalence and intensity of schistosomiasis at sentinel sites in Madagascar: Informing a national control strategy.

BackgroundSchistosomiasis affects more than 800 million people, mostly in sub-Saharan Africa. A baseline sentinel site study was conducted in the Western half of Madagascar to determine the prevalence and intensity of schistosomiasis and soil-transmitted helminth (STH) infections prior to mass drug administration, and to explore the associations between infection and school attendance, and access to water, sanitation and hygiene (WASH) facilities.MethodsA three-stage, cluster-randomised cross-sectional study was conducted in 29 sentinel sites in October 2015. Twenty school attending and 4 non-attending children in each of the age groups from 7 to 10 years old were randomly selected at each site for detection of Schistosoma haematobium eggs in a single urine slide by filtration, and of S. mansoni, Ascaris lumbricoides, Trichuris trichiura and hookworm eggs in duplicate Kato-Katz slides from a single stool sample. School attendance was registered individually, and school-level access to WASH facilities was scored through pre-defined observed and reported factors. Logistic regression analysis was performed, adjusting for gender, age and study site. School-level WASH status was analysed using Spearman’s rank correlation coefficient.ResultsA total of 1,958 children were included. The prevalence of S. haematobium infection and heavy-intensity infection was 30.5 % and 15.1 %, respectively. The prevalence of S. mansoni infection and heavy-intensity infection was 5.0 % and 0.9 %, respectively. The prevalence of any STH infection was 4.7 %. There was no significant difference in prevalence of infection or heavy-intensity infection of either schistosome species between attending and non-attending children, apart from heavy-intensity S. mansoni infection that was significantly more common in children who did not attend school regularly (aOR = 7.5 (95 % CI = 1.1-49.5); p = 0.037). Only a minority of schools had adequate access to WASH facilities, and in this study, we found no significant association between school-level WASH status and schistosomiasis.ConclusionsThis study found an alarmingly high prevalence and intensity of schistosomiasis, and the results warrant urgent scale-up of the national NTD control programme that will need to include both non-attending and attending school-age children in order to reach WHO roadmap targets for the control of schistosomiasis by 2020.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1337-4) contains supplementary material, which is available to authorized users.

Offline: The “chronic pandemic” that just won't go away

“I strongly encourage you to be cynical about the whole Sustainable Development Goal framework.” Dirk Engels is Director of the Department of Control of Neglected Tropical Diseases at WHO. He was speaking the day after a successful launch of the agency's third report on NTDs. The Bill & Melinda Gates Foundation had convened a small group at its new headquarters in London to discuss this disparate collection of 17 diseases, affecting over 1 billion people in 149 countries worldwide. The Foundation sought a vision for NTDs in the coming era of sustainable development. The tone of the conversation was sometimes pessimistic. A “nightmare”, was how one participant described the SDG landscape. But the NTD community should surely not have to worry about SDGs. They have already crafted their own Roadmap—produced by WHO in 2011, endorsed the following year by countries, donors, non-governmental organisations, and pharmaceutical companies in the London Declaration, and backed in 2013 by a tough World Health Assembly Resolution. The latest WHO report describes these extraordinary milestones as “the ‘rags to riches’ story of NTD control”. And the targets are unambiguously clear: eradication of dracunculiasis (in 2015) and yaws (in 2020); global elimination of blinding trachoma, leprosy, human African Trypanosomiasis, and lymphatic filariasis by 2020; regional elimination of selected diseases (eg, rabies and onchocerciasis in Latin America by 2015); and country elimination (eg, onchocerciasis and schistosomiasis from several countries in Africa by 2020). What more could the SDGs offer to such a well-organised international response? The answer, in one word, is money. Currently, about US$200–300 million is given for NTDs annually by donors. In 2014, the NTD community estimated that an additional US$200 million each year would be needed to meet their eradication and elimination targets. But WHO's new report cites further eye-watering figures to underline the funding challenge. Excluding medicines—thanks to generous donations by pharmaceutical companies—the total investment target for 2015–20 is US$18 billion. This massive figure is massive because it includes vector control. WHO's NTD strategy also takes advantage of the momentum behind Universal Health Coverage. Investment in universal coverage against NTDs is estimated to be US$2·1 billion annually for the entire SDG era, 2015–30. But compare these ambitious numbers to the present sobering reality. WHO ruefully notes that, “Commitments for the period 2015–2020 are currently projected at less than US$200 million per year.” Here is the reason why the SDGs are so important. Unless high-level political recognition is given to NTDs by their inclusion in new development goals, the financing to meet WHO's targets is unlikely to materialise. What are the prospects for establishing NTDs as a core element of the SDGs? Dominic Haslam, who leads policy and programmes for Sightsavers, a charity dedicated to eliminating avoidable blindness, was optimistic. NTDs were “well-placed” to be included in the post-2015 framework, he said. Christopher Fitzpatrick, an economist from WHO, pointed out that NTDs were already included in the current draft of the SDGs. Most development experts understood that NTDs were a litmus test for health equity. So what should be the specific SDG target? The target proposed, and supported at the Gates meeting, was a 90% reduction in the number of people requiring prevention of NTDs by 2030. There is no room for complacency. David Molyneux, a tenacious advocate on behalf of NTDs, argued that to strengthen political engagement these diseases should be called what they are—a “chronic pandemic”. But I left this meeting anxious about relying on the SDGs alone as a lever to pump prime funding for neglected tropical diseases. An additional objective should be the identification of a Head of State to be a standard bearer for NTDs. The UN Secretary-General himself should be encouraged to put his name and office behind WHO's Roadmap. And even if NTDs do succeed in winning an SDG target, progress will be slow without independent accountability—a mechanism to monitor and review the promises and commitments made by partners. Without a more nuanced political strategy, the NTD community's hopes of achieving either proper acceptance or new financing may need to be severely curbed.

Eradication of yaws: historical efforts and achieving WHO's 2020 target.

BackgroundYaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children's Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO's Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million.ConclusionsThe development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved.

Neglected tropical diseases: now more than just 'other diseases'--the post-2015 agenda.

Neglected tropical diseases (NTDs) have become recognised as important health problems facing at least a billion people in the low-income countries and the poorest communities in middle-income countries. WHO plays a leading role in developing strategies to address these diseases, pharmaceutical companies provide drug donations to treat or control the NTDs and many partners from different constituencies have become increasingly committed to their control or elimination. This review looks to the post-2015 agenda and emphasises that despite the progress made over recent years, if the targets established are to be achieved, then not only will additional financial resources be required to up-scale treatments and increase access, but increased applied and operational research will be necessary to address problems and human capacity in NTD skills will need to be strengthened. Continuing advocacy for the relevance of control or elimination of NTDs must be placed in the context of universal health coverage and access to donated essential medicines for the poor as a right. The evidence that investment in NTD interventions are cost-effective and impact not only on health, but also to enhance socio-economic development, must be refined and promulgated. The global burden of disease attributable to NTDs requires reassessment to appropriately define the true burden, while the potential for unexpected events, political, climatic, environmental as well as biological, have the potential to reduce future progress towards the agreed post-2015 targets. NTD progress towards the WHO Roadmap targets and the fulfilment of the World Health Assembly Resolution 66.12 of 2013 demand continued commitment from all partner constituencies when challenges emerge.

Strength in numbers? Grouping, fund allocation and coordination amongst the neglected tropical diseases.

Neglected tropical diseases (NTDs) is a term used to describe a heterogeneous group united not by pathophysiology or geography, but by their perpetuating the poverty of “invisible people”. Their burden is laid on one billion of the world’s poorest, who are both at greater risk of contracting the diseases, and of being trapped in poverty by the ensuing effects on their health [1]. The diseases tend to co–exist and can be found in 149 of the 193 countries in the world, of which 100 countries are co–endemic for at least two of the NTDs and 30 countries are endemic for six or more [2]. Photo: Graphic designed by Jennifer Matsumoto for UAEM (courtesy of the author) As use of the term “NTD” has grown in recent years, its success in collecting together a group of diseases that are largely unheard of in high–income countries and using their combined burden to give the whole group added moral, political and economic weight, has been significant. Although precise estimates vary, grouped together the NTDs have a combined global disease burden comparable to that of diseases such as tuberculosis, malaria and human–immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) [3]. This combined power has brought these diseases from the halls of global health institutions to the attention of a wide range of stakeholders including the media, politicians, philanthropists and the general public. Both scientific interest in the diseases, as measured by research publications, and internet searches for constituent diseases through Google and Yahoo!, have increased over the last decade [4]. Similarly, from 2007 to 2011, the funding for NTDs increased by over 70% [5]. However, the concept of NTDs is not being utilized to its full potential. Lobbying for funding, particularly regarding increasing access to currently available treatment, is still often done on an individual disease basis, and there is no discernible link between indicators such as research and development (R&D) funding and attributable disease burden in DALYs and deaths. Greater global coordination for the diseases, to a degree met by the London Declaration [6], may unravel with competing health issues coming to the fore and the partial completion of the main aims of the declaration. Over the past 18 months great progress has been made towards achieving the goals of the WHO roadmap to NTD control. Yet, as seen with previous control programmes, long–term international support and coordination is needed if gains are to be built upon rather than allowed to slide [7,8]. Although initiatives such as the London Declaration have improved collaboration in this field, they are limited in their scope to truly coordinate the fight against NTDs in the post–2020 era. An international coordinating committee should harness the combined power of these diseases to lobby on their behalf, collecting funds that will then be distributed on a more equitable and transparent basis, whilst ensuring the long–term monitoring and viability of programmes put in place. We aim to expand on the need for an international coordinating committee and attempt to outline the roles of such a committee.