PLOS Neglected Tropical Disease Research Articles

Bibliometrics of Cambodian Science: subjects, researchers and impact in the Science Citation Index Expanded

Introduction: Cambodia is a small agricultural tropical country for which only two small scientometric studies, published five years ago, were available until now. Objective: To identify, for Cambodian research, subjects, outlets, authors, institutions, citations and recommendations. Methods: The data were retrieved from the Science Citation Index Expanded (January 04, 2021) using the word “Cambodia” for the period 1972 to 2019. Results: We retrieved 3 689 documents: for the half century covered, the yearly presence of Cambodia in the index has grown strongly, to 325 articles and 6 555 authors in 2019 alone. Most documents are articles in English about health, particularly infectious and tropical diseases. Most international collaboration is done, by country, with the USA, France, and Thailand; and by institution, with Mahidol University, the Pasteur Institute and Oxford University. The most productive institutions are the Cambodian Ministry of Health and the Cambodian National Center for Parasitology. The main outlets are PLoS One, Malaria and PLoS Neglected Tropical Diseases. Cambodian articles are cited for up to 33 years, with a peak of 4.5 citations within the first two years. Those in English, or from well-funded foreign projects, have more citations in this particular index; especially if they are about malaria, hepatitis or influenza. Conclusions: The nature and impact of Cambodian science outside the SCI-EXPANDED remain unknown, but publications in that index have increased, concentrate on solving local problems, and depend heavily on international collaboration, following a well-known pattern of science in tropical countries. We suggest a funding system based on international peers who assign funds to the most productive researchers with minimal bureaucracy, so that local research is done on a greater variety of topics and with less participation of Cambodian researchers as low-level members in foreign projects.

The use of mobile phones for the prevention and control of arboviral diseases: a scoping review

BackgroundThe rapid expansion of dengue, Zika and chikungunya with large scale outbreaks are an increasing public health concern in many countries. Additionally, the recent coronavirus pandemic urged the need to get connected for fast information transfer and exchange. As response, health programmes have -among other interventions- incorporated digital tools such as mobile phones for supporting the control and prevention of infectious diseases. However, little is known about the benefits of mobile phone technology in terms of input, process and outcome dimensions. The purpose of this scoping review is to analyse the evidence of the use of mobile phones as an intervention tool regarding the performance, acceptance, usability, feasibility, cost and effectiveness in dengue, Zika and chikungunya control programmes.MethodsWe conducted a scoping review of studies and reports by systematically searching: i) electronic databases (PubMed, PLOS ONE, PLOS Neglected Tropical Disease, LILACS, WHOLIS, ScienceDirect and Google scholar), ii) grey literature, using Google web and iii) documents in the list of references of the selected papers. Selected studies were categorized using a pre-determined data extraction form. Finally, a narrative summary of the evidence related to general characteristics of available mobile health tools and outcomes was produced.ResultsThe systematic literature search identified 1289 records, 32 of which met the inclusion criteria and 4 records from the reference lists. A total of 36 studies were included coming from twenty different countries. Five mobile phone services were identified in this review: mobile applications (n = 18), short message services (n=7), camera phone (n = 6), mobile phone tracking data (n = 4), and simple mobile communication (n = 1). Mobile phones were used for surveillance, prevention, diagnosis, and communication demonstrating good performance, acceptance and usability by users, as well as feasibility of mobile phone under real life conditions and effectiveness in terms of contributing to a reduction of vectors/ disease and improving users-oriented behaviour changes. It can be concluded that there are benefits for using mobile phones in the fight against arboviral diseases as well as other epidemic diseases. Further studies particularly on acceptance, cost and effectiveness at scale are recommended.

Why is noma a neglected-neglected tropical disease?

Noma is an orofacial gangrene affecting primarily children living in extreme poverty in remote parts of subtropical and tropical countries. Mortality and disability are high, and survivors often have physical and functional deformities resulting in stigma and isolation. Many healthcare professionals and primary healthcare workers where noma risk factors exist have no knowledge about noma and its implications. Public health measures to improve nutrition, immunizations, sanitation, and access to healthcare and measures to eliminate extreme poverty can lead to the eradication of noma. Research allocation has been insufficient to study the epidemiology, treatment, and prevention of noma. In a recent editorial by Hotez and colleagues in PLOS Neglected Tropical Diseases (NTDs), “What constitutes an NTD?” Noma is not included. The exclusion of noma from NTDs constitutes this preventable childhood disease as a neglected neglected disease. The purpose of this article is the inclusion of noma with the PLOS NTDs. Increased awareness and attention to noma can lead to the eradication of this disease affecting the world’s most vulnerable.

A decade bibliometric analysis of global research on leishmaniasis in Web of Science database.

BackgroundLeishmaniasis is an extremely relevant tropical disease, with global distribution. It still remains a main public health concern in low-income countries, and it is necessary to support more research on this common disease. Thus, a bibliometric analysis of the global scientific production on leishmaniasis was carried out.MethodsAll the articles registered in Web of Science with the subject of leishmaniasis between 2006 and 2015 were analysed, using Pajek and VOS viewer as tools.Results13,658 records in the field of leishmaniasis were indexed in the Web of Science database for this ten-year study period (2006–2015). This shows that studies on leishmaniasis have been growing, from 1071 in 2006 to 1537 in 2015. “Sundar S” is the most active researcher in the field of leishmaniasis, compiling and participating in 232 Articles. Brazil ranks first in scientific production, by performing 3315 studies on leishmaniasis. The United States, United Kingdom and Australia had the most collaboration in performing the studies of leishmaniasis with each other. In addition, PLOS NEGLECTED TROPICAL DISEASES published the most articles, with 483.ConclusionOur data shows an increase in the number of publications in the field of leishmaniasis. In addition, Brazil, USA, and India lead scientific production on leishmaniasis research.

PLOS Neglected Tropical Diseases: Ten years of progress in neglected tropical disease control and elimination … More or less

This year PLOS Neglected Tropical Diseases (PLOS NTDs) celebrates its tenth anniversary following the publication of the first issue in 2007 [1]. When PLOS NTDs was founded, the framework of the neglected tropical diseases (NTDs) as an alternative to “other diseases” (as they were then referred to in the Millennium Development Goals) was just getting started—especially for Africa [2, 3]. In the decade since, PLOS NTDs has overseen enormous successes in NTD control and elimination. Here, we want to briefly review the ten year progress made towards the control or elimination of the diseases now identified by the WHO as NTDs. Many of the details are highlighted in PLOS NTDs papers cited here, but the summary information is based on the recently released Global Burden of Disease (GBD) Study 2015 (also launched with Gates Foundation support) that summarized past-decade changes in disease prevalence, mortality, or disability rates (from the years 2005 to 2015) [4–6], as well as the GBD Study 2013 that summarizes disease prevalence changes over a longer time horizon from 1990 to 2013 [7].

Identification and analysis of the main drivers for Ebola virus spillover

Identification and analysis of the main drivers for Ebola virus spillover

Distant peer-tutoring of clinical skills, using tablets with instructional videos and Skype: A pilot study in the UK and Malaysia

opted out of publication. Abstract #: 02ITIS023 Data sharing for neglected tropical disease drug discovery: Creating a framework for reducing redundancy and improving global collaboration M. Pollastri; Northeastern University, Boston, MA/US Program/Project Purpose: Context. With the ever widening interest in drug discovery for neglected tropical diseases, increasing numbers of academic and industrial research teams are performing medicinal chemistry optimization of potential new drug agents. One risk of this expansion is the duplication of effort caused by compartmentalized prosecution of research projects that are unknowingly focused on pursuing highly similar research directions. The root cause of this issue is the common practice of doing drug discovery research with high levels of confidentiality, a “best practice” that is typical in the for-profit pharmaceutical industry, where developing and protecting intellectual property (IP) is paramount. A new way of thinking about sharing and protecting research data for NTDs is needed. Project Period. January 2014-onward (indefinite). Why the program/project is in place. The development of a secure data sharing portal could strongly enhance and accelerate NTD drug discovery efforts worldwide, both by reducing redundancy and by engaging smaller, resource-constricted organizations who are performing drug discovery research. Aim. To establish, populate, and operate a new data sharing portal that supports drug discovery for neglected tropical diseases. Structure/Method/Design: Desired Outcomes. We intend to develop a self-sustaining, collaborative data sharing portal that captures chemical structure and biological screening data and that enables the collaborative and informed progression of NTD drug discovery projects, while balancing researchers’ desire for information protection (confidentiality). Participants: The recruitment of participants in the program has been primarily by word of mouth, utilizing social media platforms, professional scientific networks, research seminars and posters, and an opinion piece published in PLOSNeglected Tropical Diseases (DOI: 10.1371/journal.pntd.000286). Sustainability: Viability will be dictated by: (1) Engagement. We plan to have r portal teleconference meetings to discuss recent deposits and ongoing projects. In addition, we aspire to make available unique research resources for participating members in order to incentivize active participation. (2) Funding: we will seek funding from other organizations (NIH, BMGF) in order to further operate the portal. Outcomes & Evaluation: Successes We have secured $25,000 in funding via crowdfunding and established the database. We have also identified large tranches of data for deposit and shared, and have engaged other academic NTD drug discovery groups Monitoring. None conducted. Going Forward: Ongoing challenges? The primary challenge has been to recruit participants who will deposit data into the portal and agree to deposit new data on an ongoing basis. Are there any unmet goals? No How are/may future program activities change as a result? N/A Funding: The pilot phase of this project has been funded by a crowdfunding campaign ($25,000): Abstract #: 02ITIS024 An assessment of data quality in Haiti’s multi-site electronic medical record system N. Puttkammer, J. Baseman, B. Devine, N. Hyppolite, G. France, J. Honore, A. Matheson, S. Zeliadt, K. Yuhas, K. Sherr, J. Cadet, S. Barnhart; University of Washington, Seattle, WA/US, University of Washington, Seattle, WA/US, International Training and Education Center for Health (I-TECH)–Haiti, Port-au-Prince, Haiti, Ministry of Health and Population (MSPP), Port-au-Prince, Haiti, National Program for Control of Malaria (PNCM), Port-au-Prince, Haiti Background: The World Health Organization has identified health information systems as a “building block” for health systems

Has the NTD Community Neglected Evidence-Based Policy? PLOS NTDs 2013 Expert Commentary of the Viewpoint by Nagpal S, Sinclair D, Garner P

In July 2013, PLOS Neglected Tropical Diseases will publish the viewpoint of members of the Cochrane Infectious Diseases Group [1] on the scientific evidence supporting the public-health benefits of preventive chemotherapy [2] in the case of programmes against neglected tropical diseases (NTDs), specifically those for the control and elimination of lymphatic filariasis, onchocerciasis, schistosomiasis, and soil-transmitted helminthiases. This viewpoint presents the group's interpretation of its findings on health interventions using Cochrane systematic reviews of preventive chemotherapy interventions published in recent years, which do not confirm the benefits of the intervention at the community level [3], [4]. However, these reviews were conducted by analyzing data exclusively from randomized controlled trials (RCTs). WHO considers RCTs study designs that have been developed to compare drug efficacy over short-term periods and that are not appropriate for evaluating interventions such as preventive chemotherapy, which should be applied to a population for at least five consecutive years [5]. The main reason for this is that it is almost impossible to organize proper RCTs for preventive chemotherapy interventions because of ethical reasons (it is not ethically acceptable to exclude infected populations from treatment for five years). In addition, the results of RCTs are analyzed on the assumption that because preventive chemotherapy is applied at population level, its benefits should be observed in the entire population; by doing so, the key point is missed: that this strategy is used not because it will benefit the uninfected, but because it is more cost-effective to treat everyone than to select those who are infected [6]. In our view, the limitations of RCTs (and reviews based exclusively on their analysis to conclude on public-health interventions) are proven by the fact that they consistently confirmed the efficacy of preventive chemotherapy medicines (albendazole, mebendazole, praziquantel, ivermectin, and DEC) against the parasites targeted (because RCTs are designed to evaluate such results) but failed to demonstrate their impact on communities (because RCTs are not designed to measure such impacts). We consider the best way to evaluate the benefits of preventive chemotherapy interventions to be through monitoring the impact of a disease control or elimination programme for several years. Whenever long-term interventions are evaluated, the impact of preventive chemotherapy on morbidity is evident. For example, Ramzy et al. [7] showed that five annual rounds of mass drug administration eliminated lymphatic filariasis in endemic communities in Egypt; Traore et al. [8] proved that elimination of onchocerciasis with ivermectin is technically feasible in hyperendemic foci from Mali and Senegal; Sinoun et al. [9] demonstrated the complete elimination of the morbidity caused by schistosomiasis in Cambodia after an eight-year intervention; and Casey et al. [10] showed successful control of soil-transmitted helminthiases and improved haemoglobin levels after 56 months of activities in Viet Nam. Unfortunately, none of these articles merited attention by the authors of this viewpoint, probably because they are not RCTs. We therefore consider the conclusion of the authors of this viewpoint the consequence of a selection bias. Some studies demonstrated that preventive chemotherapy is beneficial not only for the populations targeted but also for future generations: for example, Ottesen et al. [11] calculated that, between 2000 and 2007, mass drug administration prevented lymphatic filariasis in 6.6 million newborns, thus averting in their lifetimes nearly 1.4 million cases of hydrocele, 800,000 cases of lymphoedema, and 4.4 million cases of subclinical disease. In addition, evidence demonstrates that preventive chemotherapy is beneficial for diseases that are not included in WHO's list of neglected tropical diseases, such as scabies, which benefit from the large-scale application of ivermectin [12], and to mortality in general, which was significantly reduced in Ethiopia by the large-scale distribution of azithromycin [13]. Finally, it seems to us ethically unacceptable that infected human populations are not administered medication that is freely available while livestock and companion animals are regularly dewormed every year.

Has the NTD community neglected evidence-based policy?

Over the past decade, systematic reviews and explicit evidence-based approaches have replaced expert opinion as the basis for health policy [1]. In developing countries, the high disease burden coupled with limited financial resources for health requires governments, donors, and the public to choose between competing public health and clinical care options, and increasingly they turn to ‘‘evidence’’ to inform these decisions. Systematic reviews of the benefits and harms of different policies and treatments are one of the core sources of evidence, providing concise summaries of the available research about effects [2]. Wellconducted systematic reviews aim to minimize bias in presenting and interpreting results. This can arise due to intentional or unintentional selective studies inclusion, selective reporting, uncritical reading of poorly conducted trials, and incorrect inferences from the data across studies [3]. Alongside evidence on effects, decision making requires other information including cost, disease burden, and the acceptability and feasibility of the policy options. Nevertheless, data on effects is fundamental, because if something does not work, it will not impact on health, and it is not cost-effective, irrespective of whether the drug is cheap or expensive. As members of the Cochrane Infectious Diseases Group, we have, over the past twenty years, seen steady growth in the demand for systematic reviews to inform international and national policy decisions in infectious diseases. Our reviews have been used by policy makers as they have made recommendations to scale-up impregnated mosquito nets [4], reintroduce amodiaquine for malaria [5], change the formula of ORS [6], and switch to artesunate for severe malaria [7]. However, not all our systematic reviews support current policies; some identify research gaps, and some cast doubt on the benefits of the interventions. These gaps may indicate further research is required before these interventions can be recommended. The most complicated policy situations are those in which there is limited evidence of public health benefit, yet statements made by experts recommend the policy. If indeed the expert opinion is wrong, then the continued delivery of the intervention may waste public resources, or fail to bring about all of the promised benefits. One such example of a current debate is in routine deworming of all schoolchildren in areas where intestinal helminths occur. The Cochrane review, in light of current guidelines, advocacy, and policies, represents an area where assumed benefit by expert panels is by no means supported by quite a lot of available, reliable research [8]. Whatever the outcome of future recommendations from the World Health Organization and others is, what is important is that independent syntheses by groups external to the advocacy provide reliable summaries that can be considered in decision making. We are concerned that the neglected tropical disease (NTD) academic community has been slow to engage in evidenceinformed policy and debate, and may be falling behind international best practice. This is borne out of a concern that NTDs are important diseases that need treatments, but that international policies need to stay in line with current international expectations of evidence-informed policy to avoid being discredited. To look for evidence to confirm or refute these concerns, we used appropriate systematic methods (Text S1), and present our interpretation of these data as a viewpoint at the request of PLOS NTDs editors. Influential Papers in NTD Policy and the Evidence They Cite

“Barriers" to Child Development and Human Potential: The Case for Including the “Neglected Enteric Protozoa" (NEP) and Other Enteropathy-Associated Pathogens in the NTDs

The World Health Organization (WHO) has set forth ambitious efforts to control, and where possible, eliminate the neglected tropical diseases (NTDs) that contribute to poverty and “impair the ability of those infected to achieve their full potential, both developmentally and socio-economically [1], [2]. This neglected disease initiative's (NDI) purpose has been to close the existing poverty gap between individuals living in low/middle-income and high-income countries, and thus facilitate the achievement of the 2000 Millennium Developmental Goals [3]. The gap is still large. Yet, some marked achievements of the NDI, including coordinated administration of preventive chemotherapy to nearly 670 million children globally and the imminent elimination of dracunculiasis, give hope that the WHO's NTD paradigm, a “five-pronged approach of 1) preventive chemotherapy, 2) intensified case-management, 3) vector control, 4) provision of safe water, sanitation, and hygiene, and 5) veterinary public health, are proving beneficial [1]. Malnutrition and unfulfilled human potential are widely prevalent among the 1.4 billion people also afflicted by the principal NTDs. Over the last decade, we have become increasingly aware that alterations in intestinal function not only associate with malnutrition, but are likely one of its driving forces. It was recognized half a century ago that children in developing countries had intestinal mucosa that showed morphological flattening [4] and malabsorption [5] that were reversible upon exposure to a cleaner environment. Similarly, Lindenbaum also showed in the 1960s that Peace Corps volunteers with diarrhea and malnutrition had biochemical markers of malabsorption: 40% had decreased d-xylose levels, and 52% had low Schilling tests. Moreover, 88% of intestinal biopsies from these volunteers showed mild to moderate jejunitis with decreased villus∶crypt ratios [6]. Villus blunting along with chronic inflammation associates with impaired intestinal barrier function with resultant increased intestinal permeability [7]. This combination of altered villus architecture and barrier function, so uniquely dependent upon one's environment, has been termed “environmental (EE) [8]. These characteristic EE changes have been epidemiologically linked with growth faltering and are one hypothesis for why intensive nutritional supplementation interventions done under even ideal clinical trial conditions have significant but limited success in improving weight, linear growth, and cognitive function [9]–[11]. Syndemic with environmental enteropathy are high rates of childhood diarrhea. Although children may display “catch-up growth following isolated and short-lived (3 days) diarrheal episodes [12], prolonged and persistent diarrheal (>14 days) episodes strongly associate with stunting [13]–[16]. Testament to the effectiveness of WHO campaigns, the combination of oral rehydration solution (ORS) in the 1980s and its subsequent refinements, and the introduction of rotavirus vaccines in some populations [17], have led to significant reductions in diarrhea-related mortality from 4.5 million/year over a decade ago to 1.5 million/year in 2010 [18], [19]. Currently, however, there are still >700,000 deaths per year globally related to diarrheal diseases [20], and conversely, the frequency of diarrheal episodes has not declined but remains unacceptably high [21]. Among the myriad pathogens causing diarrhea in low/middle-income countries, the Giardia lamblia (synonymous with G. intestinalis/G. duodenalis) and Cryptosporidium spp. are among the most commonly isolated [22]. Although present in PLOS NTDs' expanded NTD list [23], and added to the WHO's NDI in 2004 [2], [24], these organisms are not mentioned in the 2010 WHO NTD report [1]. Despite the call for increased surveillance [2], the true global prevalence of these infections remains poorly defined [25]. In the past few years, we have learned important lessons that make imperative an emphasis on these “neglected enteric protozoa (NEP) and other enteropathy-associated pathogens within the NDI: The enteric should be classified with the soil-transmitted helminths (STHs) as pathogens associated with stunting. We need to restructure our theoretical framework to broaden our concept of “diarrheal disease to include “asymptomatic enteric infections. We must recognize that environmental enteropathy is likely both a common and complex disease, and that infections related to the development or exacerbation of environmental enteropathy deserve prioritization in disease control strategies. Therapeutic strategies against enteropathy-associated pathogens can and should be evaluated for efficacy within the existing NDI programs.

Now We Are Six

Now We Are Six

A New Clinical Section in PLoS Neglected Tropical Diseases

PLoS Neglected Tropical Diseases (PLoS NTDs) provides a platform of information that links multiple scientific disciplines in the battle against the substantial public health and economic impact imposed by neglected tropical diseases (NTDs). The types of articles published in PLoS NTDs include health policy; control, elimination, and eradication programs; epidemiological and operational research; basic pathobiology, translational research, and development; development of new diagnostic tests; and many other areas of action. PLoS NTDs also reaches health care practitioners caring for individuals suffering from NTDs through the clinical symposium section. To effectively target this audience, the clinical symposium section delivers critical information in the case management of NTDs backed by the expertise and commitment of our clinician editors. Up until now, the clinical symposium section has included two types of article formats: a case-report format, and case-based learning articles that consist of a question and answer format illustrating key clinical issues in the diagnosis and management of NTDs. Both types of articles are presented in a simple format that makes them easy to apply to direct patient care with an emphasis on key learning points to provide clinical pearls or take-home points. In this issue of PLoS NTDs, we are pleased to launch a new section to complement the clinical symposium section with the publication of the first Photo Quiz. Our first Photo Quiz case addresses the diagnosis and management of actinomycetoma in both resource-rich and resource-poor settings [1]. This new clinical section is devoted to question-and-answer challenges through the use of specific NTD clinical images, each illustrating a key clinical finding in the diagnosis, management, or prevention of a selected disease. We encourage the audience of clinical practitioners to submit relevant clinical, radiographic, or microbiological images. Some examples may include images of a clinical sign characteristic of infection with a particular pathogen; radiographic images that may be identified in patients suffering from a particular NTD; electrocardiograms or echocardiograms with relevant abnormalities; or a video of the patient's clinical signs. From a laboratory/pathology perspective, we also encourage submission of pathogens identified in clinical specimens. All images will be published under the Creative Commons Attribution License (http://www.plosntds.org/static/license.action), followed by discussion of key learning points. Upon submission of a manuscript, cases will be assessed by the editorial office and subsequently undergo a formal peer review process following the PLoS NTDs editorial review policy (http://www.plosntds.org/static/guidelines.action#overview). Submissions for the Photo Quiz section should follow the two-part format outlined in Box 1. Box 1. Instructions for Photo Quiz Submissions A. Case Discussion and Question The submitter(s) should provide an initial brief presentation of a clinical case (history, physical examination, relevant laboratories, etc.) with key clinical images, which should invite a diagnosis from the reader by posing a single-sentence question about the case. The case presentation and question should be written in a single paragraph and should be accompanied by no more than 2 images/figures (no more than 150 words). Similar to the Symposium manuscripts, authors must obtain written consent from the patient using our consent form (also available in French, Portuguese, and Spanish). Consent forms are available at http://www.plosntds.org/static/guidelines.action#supporting. B. Answer(s)/Discussion The answer should give the diagnosis followed by a discussion of the most relevant clinical issues (no more than 1,200 words). C. Key Learning Points Authors must include a box that lists 3–5 key learning points of the case similar to other clinical sections of PLoS NTDs. D. References No more than 10 references.

PLoS Biology at 5: The Future Is Open Access

PLoS Biology at 5: The Future Is Open Access

The Giant Anteater in the Room: Brazil's Neglected Tropical Diseases Problem

The Giant Anteater in the Room: Brazil's Neglected Tropical Diseases Problem

Poverty, Human Development, and Basic Biology

Poverty, Human Development, and Basic Biology