Unequal Distribution of Innovation Efforts for Neglected Tropical Diseases: The Role of Funding Evaluation Criteria

Background: International research and innovation efforts for neglected tropical diseases have increased in recent decades due to disparities in overall health research funding in relation to global burden of disease. However, within the field of neglected tropical diseases some seem far more neglected than others. In this research the aim is to investigate the distribution of resources and efforts, as well as the mechanisms that underpin funding allocation for neglected tropical diseases. Methodology: A systematic literature review was conducted to establish a comprehensive overview of known indicators for innovation efforts related to a wide range of neglected tropical diseases. Articles were selected based on a subjective evaluation of their relevance, the presence of original data, and the breadth of their scope. This was followed by thirteen in-depth open-ended interviews with representatives of private, public and philanthropic funding organizations, concerning evaluation criteria for funding research proposals. Results: The findings reveal a large difference in the extent to which the individual diseases are neglected with notable differences between absolute and relative efforts. Criteria used in the evaluation of research proposals relate to potential impact, the probability of success and strategic fit. Private organizations prioritize strategic fit and economic impact;philanthropic organizations prioritize short-term societal impact;and public generally prioritize the probability of success by accounting for follow-up funding and involvement of industry. Funding decisions of different types of organizations are highly interrelated. Conclusions: This study shows that the evaluation of funding proposals introduces and retains unequal funding distribution, reinforcing the relative neglect of diseases. Societal impact is the primary rationale for funding but application of it as a funding criterion is associated with significant challenges. Furthermore, current application of evaluation criteria leads to a primary focus on short-term impact. Through current practice, the relatively most neglected diseases will remain so, and a long-term strategy is needed to resolve this.

国内外医药期刊载文及被引用情况对比及分析——以《Asian Pacific Journal of Tropical Medicine》与《PLoS Neglected Tropical Diseases》为例

《Asian Pacific Journal of Tropical Medicine》是中国唯一一本被美国科学引文索引(SCI)数据库收录的全英文版热带医药期刊。文章通过Web of Science数据库对《Asian Pacific Journal of Tropical Medicine》2008-2012年载文及被引用情况进行了统计,并与国际热带医药杂志《PLoS Neglected Tropical Diseases》进行比较。结果显示,《Asian Pacific Journal of Tropical Medicine》与《PLoS Neglected Tropical Diseases》在IF值、载文量、被引总频次、每项平均引用次数、h指数等各方面都存在显著差距,杂志需不断加强组稿,完善审稿评议流程,缩短出版周期,建立出版后信息反馈制度,以提高杂志的学术质量和国际影响力。

Cutaneaous Myiasis: A Rare Tropical Disease in an 11-Year-Old Girl

Myiasis is the infestation of live human and vertebrate animals with maggots that feed on the host’s dead or living tissue, depending on the life cycle of the fly. It is a rare condition and often misdiagnosed. Tropical and subtropical regions of the world are commonly affected. The aim of this case report is to share this uncommon cutaneous condition with health workers and also remind them of its common symptoms and signs such that its diagnosis is not missed. An 11-year-old girl presented with a nine-day history of itchy rash involving mainly the trunk and upper arms which were found to be cutaneous Myiasis. Cutaneous Myiasis can cause miserly to the affected individual due to its symptoms, yet it can be prevented with good environmental and personal hygiene. Diagnosis and treatment are cheap and effective.

Antibacterial activity of leaves extracts of Trifolium alexandrinum Linn,against pathogenic bacteria causing tropical diseases

Objective:To investigate antibacterial potential of Trifolium alexandrinum(T.alexandrinum) Linn,against seven gram positive and eleven gram negative hospital isolated human pathogenic bacterial strains responsible for many tropical diseases.Methods:Non-polar and polar extracts of the leaves of T.alexandrinum i.e.,hexane,dichloromethane(DCM),ethyl acetate(EtOAc), methanol(MeOH) and aqueous(AQ) extracts at five different concentrations(1,2,5,10 and 15 mg/ mL) were prepared to evaluate their antibacterial value.NCCL standards were strictly followed to perform antimicrobial disc susceptibility test using disc diffusion method.Results:Polar extracts demonstrated significant antibacterial activity against tested pathogens.EtOAc and MeOH extracts showed maximum antibacterial activity with higher inhibition zone and were found effective against seventeen of the tested pathogens.While AQ plant extract inhibited the growth of sixteen of the test strains.EtOAc and MeOH plant extracts inhibited the growth of all seven gram positive and ten of the gram negative bacterial strains.Conclusions:The present study strongly confirms the effectiveness of crude leaves extracts against tested human pathogenic bacterial strains causing several tropical diseases.Since Egyptian clover is used as a fodder plant,it could be helpful in controlling various infectious diseases associated with cattle as well.

Demographic,socioeconomic and environmental changes affecting circulation of neglected tropical diseases in Egypt

Egypt has been plagued by many neglected tropical diseases since Pharaonic time.These diseases are Schistosomiasis.soil transmitted helminthiasis,lymphatic filariasis.leishmaniasis and fascioliasis beside the epidermal parasitic skin diseases.Indeed,theses disease still persist as public health problem in the country by the influence of demographic,socioeconomic and environmental obstacles.This study seeks for understanding the contribution of each factor in each obstacle in neglected tropical diseases perpetuation which in turn could help the governorate in planning integrated control strategies.It was found that poverty,unregulated urbanization and inadequate sanitation are important socioeconomic factors that have great effect on the transmission dynamics of the disease.The environmental factors which affect the epidemiology of these diseases in the counln are scarcity of water,construction of dams,land reclamation for agriculture beside the climate factors.Unfortunately.the panic increase in the population growth rale minimizes the efforts done by the governorate to elevate the public health services.These conditions also affect the transmission of epidermal parasitic skin diseases including scabies,head lice and hookworm—related cutaneous larva migrans.The control programs and the recommendations to combat the diseases were discussed.The present study showed that the ecological factors affecting each neglected tropical disease in Egypt are somewhat similar which makes it worthy to develop an integrated control approaches aiming at improving the leading factors of neglected tropical diseases circulation in the country.

Vector-borne diseases: Mosquito holobiont and novel methods for vector control

Female mosquitoes of several species require blood from warmblooded animals,including humans for the purpose of reproduction.In this process,several microbes residing in the salivary gland and midgut of mosquitoes also get transferred from one human individual to the other–a traditional model by which many vector-borne diseases(VBDs)get transmitted in the population through mosquitoes belonging to Anopheles,Aedes,Culex and other genera.

An Agent-Based Model for Studying the Impact of Herd Mobility on the Spread of Vector-Borne Diseases: The Case of Rift Valley Fever (Ferlo Senegal)

Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.

Serological investigation of vector-borne disease in dogs from rural areas of China

Objective:To evaluate the Anaplasma phagocytophilum(A.phagocytophilum),Ehrlichia canis(E.canis,Dirofilaria immitis(D.immitis)(canine heartworm),Borrelia burgdorferi(B.burgdorferi)infections in countryside dogs from Yunnan,Hainan and Anhui provinces.Methods:Serum samples were collected from 26 dogs in Yunnan.Hainan and Anhui provinces.The samples were tested using a commercial ELISA rapid diagnostic assay kit(SNAP^(?)4Dx^(?);IDEXX Laboratories,Inc.U.S.A.).Meaiiwliile,indirect immunofluorescence assay(IFA)recommended by WHO was conducted to delect IgG to A.phagocytophilum.Two methods were analyzed and compared.Results:The number of serologically positive dogs for IgG to A.phagocytophilum was only 2which was from Hainan province and none of the 26 dogs responded positive for E.canu.D.immitis(canine heartworm,and B.burgdorferi by ELISA rapid diagnostic method.The number of serologically positive dogs for IgG to A.phagocytophilum was 13(50%)by IFA method.Data of the two methods were analyzed by statistical software and the difference was statistically significant(P=0.002).Conclusions:It can be concluded that IFA method was more sensitive than ELISA rapid diagnostic method.However,we need conduct further and intensive epidemiology survey on tick-born diseases pathogens including.4.phagocytophilum,E.canis,D.immitis(canine heartworm),and B.burgdorferi which have public health significance.

Global Dynamic Analysis of a Vector-Borne Plant Disease Model with Discontinuous Treatment

This paper proposes a vector-borne plant disease model with discontinuous treatment strategies. Constructing Lyapunov function and applying non-smooth theory to analyze discontinuous differential equations, the basic reproductive number R0 is proved, which determines whether the plant disease will be extinct or not. If R0 R0 > 1 , there exists a unique endemic equilibrium which is globally stable. The numerical simulations are provided to verify our theoretical results, which indicate that after infective individuals reach some level, strengthening treatment measures is proved to be beneficial in controlling disease transmission.

Anisakiasis in Southeast Asia: A story of new tropical disease?

Anisakiasis is an important worm infestation. It is seen in some non-tropical countries and becomes an important issue in coastal medicine. However, in the few recent years, there are some reports on occurrence of anisakiasis in tropical countries. In this specific short article,the authors review and present the situation of anisakiasis in Southeast Asia. It can be said that anisakiasis becomes a new focused interest in tropical coastal medicine at present.

Choice of providers for treating a neglected tropical disease:an empirical analysis of kala azar in Nepal

Objective:To examine the choice of healthcare providers for treating kala azar(KA) in Nepal. Methods:Information was collected from clinically diagnosed KA patients seeking care from public hospitals located in KA endemic districts.The survey collected information from more than 25 percent of total KA cases in the country.For empirical estimation of probability of choosing a provider-type as a first contact healthcare provider,a multinomial logit model was defined with five alternative options with self care as the reference category.Results:The empirical model found that price of medical care services,income of households,knowledge of patients on KA and KA treatment,borrowing money,age of patient,perceived quality of provider types,etc.determine the likelihood of seeking care from the alternative options considered in the analysis.All variables have expected signs and are con.vstent with earlier studies.The price and income elasticity were found to be very high indicating that poorer households are very sensitive to price and income changes,even for a severe disease like KA.Using the empirical models, we have analyzed two policy instruments:demand side financing and interventions to improve the knowledge index about KA.Conclusions:Due to high price elasticity of KA care and high spillover effects of KA on the society,policy makers may consider demand side financing as an instrument to encourage utilization of public hospitals.

Potential of herbal constituents as new natural leads against helminthiasis: A neglected tropical disease

The WHO reports that billions of people and animals in tropical and subtropical regions are affected by helminthiasis as neglected tropical disease. It is predominant in underdeveloped areas;nevertheless, the increase in the number of travelers and migrants has made this infection more common. The current mass drug treatment produces severe side effects and many strains of helminths are resistant to them. None of the chemotherapeutic drugs meets the ideal requirements of anthelmintics, such as broad spectrum of activity, single dose cure, free from side effect and cost-effectiveness. Today, many researchers are screening the traditional herbal system in search of the anthelmintic herbal constituents which overcome all the problems of synthetic drugs. Several researchers proclaim anthelmintic activity of herbal medicines by using different experimental models. The present review demonstrates natural product drug discovery, outlining potential of herbal constituents from natural sources as natural leads against helminthiasis.

Adult Onset Still’s Disease in Tropical Area: Illustration of Diagnostic and Therapeutic Difficulties from 3 Senegaleses Observations

Introduction: The Adult Onset Still’s Disease (ASD) is a systemic auto-inflammatory affection of unknown cause seldom described in sub-Saharan Africa. We report 3 observations of ASD illustrating the diagnostic and therapeutic difficulties of this affection in our areas. Observation 1: Our first patient is a 56 years old schoolteacher presenting an ASD in its chronic articular form. She had been followed for an inflammatory arthralgia for 10 years and of the pharyngal pains without exact diagnosis. She presented ASD’s criteria of Yamaguchi and of Fautrel. The prednisone was begun at the dose of 0.8 mg/kg/day with fast appearance of a progressive muscular weakness. Use of methotrexate at a rate of 15 mg per week, associated with low dose of prednisone was effective in long-term without any flare of the disease so far. Observation 2: Our second patient is a 30 years old dressmaker presenting an ASD in its complicated systemic form of lymphohistiocytic activation syndrome. She validated the criteria of Yamaguchi and Fautrel for ASD. She also presented resistance to corticosteroid therapy. The evolution was marked by a hospital-acquired septicemia and a multi-organ failure leading to death. The diagnosis was retrospectively confirmed after that, with the low level of the glycosylated ferritin serum value. Observation 3: The third patient is a 22 years old Guinean student who presented prolonged fever and inflammatory polyarthralgia without articular deformation. He had been misdiagnosed for ASD with diagnostic wandering of several months. He was treated successfully with prednisone after set up of ASD diagnosis according common criteria. Corticosteroid therapy was stopped after 8 months without any relapse noted so far. Conclusion: Caring for ASD is difficult in our context mainly because of high cost of several explorations needed to set up its exact diagnosis while making differential one. Evolution under corticosteroid therapy is usually favorable but diagnostic delay may lead to severe complications and death.

Effective Control Strategies on the Transmission Dynamics of a Vector-Borne Disease

In this paper, we have rigorously analyzed a model to find the effective control strategies on the transmission dynamics of a vector-borne disease. It is proved that the global dynamics of the disease are completely determined by the basic reproduction number. The numerical simulations (using MatLab and Maple) of the model reveal that the precautionary measures at the aquatic and adult stage decrease the number of new cases of dengue virus. Numerical simulation indicates that if we take the precautionary measures seriously then it would be more effective than even giving the treatment to the infected individuals.

Study on Control Effect of Invasive Banana Fusarium Disease(Fusarium oxysporum f.sp.cubense tropical race 4)by Different Varieties and Fertilization Treatments

[Objective]The paper was to understand the field resistance performance of different banana varieties and the prevention and control ef-fect of different fertilizers,so as to provide technical reference for the prevention and control of Fusarium wilt.[Method]Field trials were set up with three treatments:shrimp peptide organic fertilizer+shrimp peptide special protection+shrimp peptide fruit Yekang(simplified as shrimp peptide organic fertilizer treatment),conventional organic fertilizer+microbial preparations(simplified as microbial treatment),and conventional or-ganic fertilizer(simplified as control).Four different banana varieties of Brazilian banana,Guijiao No.1,Nantianhuang,and Yunjiao No.1 were se-lected for the field trial.The disease incidence of Fusarium wilt and the control effects of three fertilizers were investigated during four time periods.[Result]The disease incidence of four varieties in three treatments varied.The disease incidence of Nantianhuang and Yunjiao No.1 were signifi-cantly lower than that of other two varieties.There was also significant difference in disease incidence of three treatments.The disease incidence from high to low was control>shrimp peptide organic fertilizer treatment>microbial treatment.The average monthly TR4 pathogen content in heavily infected banana plantation was more than 2000 copies,while the highest one reached 15148.9 copies.[Conclusion]Microbial agents reduced the disease incidence of Fusarium wilt to some content.Nantianhuang and Yunjiao No.1 showed the highest disease resistance compared with other varieties.However,their resistance needs to be further improved before practical application.

Asymptotic Analysis of a Stochastic Model of Mosquito-Borne Disease with the Use of Insecticides and Bet Nets

Ross’ epidemic model describing the transmission of malaria uses two classes of infection, one for humans and one for mosquitoes. This paper presents a stochastic extension of a deterministic vector-borne epidemic model based only on the class of human infectious. The consistency of the model is established by proving that the stochastic delay differential equation describing the model has a unique positive global solution. The extinction of the disease is studied through the analysis of the stability of the disease-free equilibrium state and the persistence of the model. Finally, we introduce some numerical simulations to illustrate the obtained results.

Genetic mechanisms underlying the pathogenesis of tropical calcific pancreatitis

Chronic pancreatitis is known to be a heterogeneous disease with varied etiologies.Tropical calcific pancreatitis(TCP) is a severe form of chronic pancreatitis unique to developing countries.With growing evidence of genetic factors contributing to the pathogenesis of TCP,this review is aimed at compiling the available information in this field.We also propose a two hit model to explain the sequence of events in the pathogenesis of TCP.

DNA methylation patterns of banana leaves in response to Fusarium oxysporum f. sp. cubense tropical race 4

Fusarium wilt of banana, which is caused by Fusarium oxysporum f. sp. cubense tropical race 4 （Foc TR4）, is a serious soil-borne fungal disease. Now, the epigenetic molecular pathogenic basis is elusive. In this study, with methylation-sensitive amplification polymorphism （MSAP） technique, DNA methylation was compared between the leaves inoculated with Foc TR4 and the mock-inoculated leaves at different pathogenic stages. With 25 pairs of primers, 1 144 and 1 255 fragments were amplified from the infected and mock-inoculated leaves, respectively. DNA methylation was both changed and the average methylated CCGG sequences were 34.81 and 29.26% for the infected and the mock-inoculated leaves. And DNA hypermethylation and hypomethylation were induced by pathogen infection during all pathogenic stages. Further, 69 polymorphic fragments were sequenced and 29 of them showed sequence similarity to genes with known functions. And RT-PCR results of four genes indicated that their expression patterns were consistent with their methylation patterns. Our results suggest that DNA methylation plays important roles in pathogenic response to Foc TR4 for banana.

Infectious diseases during the European Union training mission Mali(EUTM MLI)–a four-year experience

Background: The European Union Training Mission Mali(EUTM MLI) is a multinational military training deployment to the Western African tropical nation of Mali. Based on routinely collected disease and non-battle injury surveillance data, this study quantifies the true impact of infectious diseases for this tropical mission and potential seasonal variations in infectious disease threats.Methods: Categorized health events during the EUTM MLI mission and associated lost working days were reported using the EpiNATO-2 report. Infection-related health events were descriptively analyzed for a 4-year period from the 12 th week in 2013 to the 13 th week in 2017. Aggregated EpiNATO-2 data collected from all missions other than EUTM MLI were used as a comparator.Results: Among the infectious diseases reported by EUTM MLI, non-severe upper respiratory infections and gastrointestinal diseases dominated quantitatively, accounting for 1.65 and 1.42 consultations per 100 person-weeks, respectively. The number of recorded infectious disease-associated lost working days during the whole study interval was 723. Seasonal changes in disease frequency were detectable. More gastrointestinal infections were seen in the rainy season, and more respiratory infections occurred in the dry season; these were associated with peaks of more than 2.5 consultations per 100 person-weeks for both categories.Conclusion: Despite initial concerns focused on tropical infectious diseases during this mission in tropical Mali, upper respiratory tract and gastrointestinal infections predominate. The relatively low number of reported lost working days may indicate that these infections are at the milder end of the spectrum of infectious diseases despite a likely reporting bias.

Risk factors for peripheral arterial disease in the tropics and its comparison with the western population

Objective:To identify and compare the existence of similar and other risk factors in the perspective of an Indian population.Methods:It was designed as a case control study and was conducted in the Department of General and Vascular Surgery Unit 2 of Christian Medical College,Vellore,India between the periods July 2003 to June 2005.100 patients with an ABPI【 0.9 and 100 controls were studied.Results:Peripheral arterial disease(PAD) was found to be commoner among males(87%).While atherosclerosis was the commonest aetiology(54%),the incidence of Thromboangiitis Obliterans was also not uncommon(38%).Smoking was the main risk factor in the Indian context(83%) as compared to hypercholesterolemia(60%) in the West. The patients with atherosclerotic PAD were middle-aged and had concomitant diabetes(50%) and hypertension(30%).Conclusions:Peripheral arterial disease occurs in a relatively younger age group in India as compared to their Western counterparts.Thromboangiitis Obliterans was found to be a significant aetiology for arterial occlusive disease,with smoking as the primary risk factor followed by diabetes,hypertension and hypercholesterolemia.