Throughout history, traditional herbal medicine has afforded a rich repository of remedies with diverse chemical structures and bioactivities against several health disorders. A common issue of herbal medicine is the limitation of information on their pharmacological activities and their active constituents. Traditionally, the use of herbal medicine has been based on empirical treatment and passed on from generation to generation with information available only in local journals. This prevents several herbal medicines from being developed to their full potential. The presentation will focus on research and development of Atractylodes lancea (Thunb) DC. (AL: family Compositae) as a potential chemotherapeutic for cholangiocarcinoma (CCA), the bile duct cancer commonly found in Southeast Asia. The dried rhizome of AL is a medicinal plant used in Chinese (“Cang Zhu”), Japan (“So-jutsu”) and Thai (“Khod-Kha-Mao”) traditional medicine for its various pharmacological properties including anticancer, anti-inflammation and antimicrobial activities, activities on central nervous, cardiovascular, and gastrointestinal systems. The major constituents in the essential oils from AL rhizome are β-eudesmol, hinesol and atractylon. Preliminary investigation has demonstrated its promising anti-CCA activity both in vitro and animal (Opisthorchis viverrini/dimethylnitrosamine-induced CCA in hamsters and CCA—xenografted nude mice) models with high selectivity index comparing with the standard drug, 5-fluorouracil. It also showed virtually no toxicity with only minimal CNS effects on locomotor activity at the maximum dose of 5,000 mg/kg body weight. Studies are underway to identify active constituent(s) which contribute to anti-CCA activity as well as its pharmacokinetic and pharmacodynamic properties. The main research interest of my research group is the discovery and development of traditional herbal medicine for the treatment of two important tropical diseases, cholangiocarcinoma and malaria. As the time is quite limited, I am going to give you the summary of the conceptual framework and highlight some important findings which will illustrate how different approaches have been used or applied for the discovery of the promising candidates for these two diseases.

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Epidermal parasitic skin diseases (EPSD) are common in the tropics and sub-tropics. They are caused by mites, lice and other blood-sucking insects. In resource-poor countries they are associated with considerable morbidity. Hitherto, EPSD are treated with insecticides with a neurotoxic mode of action. The efficacy of this treatment is variable, and the development and spread of resistant mites and lice is alarming.A new concept for treating EPSD is presented which is based on the topical application of dimeticones, silicone oils of low viscosity which rapidly kill insects and mites by a physical mode of action. They creep into the respiratory system and block oxygen supply. The physical mode of action makes the development of resistant parasite strains very unlikely. Due to their safety and efficacy, dimeticones are promising candidates for population-based intervention programmes targeted against EPSD in resource-poor settings.

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Lymphatic filariasis is one of the neglected tropical diseases. It is estimated that 120 million people are currently infected in 73 countries where filariasis is endemic. Lymphatic filariasis is a leading cause of chronic disability worldwide, including of 15 million people who have lymphoedema (elephantiasis) and 25 million men who have hydrocoele.

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The World Health Organization (WHO) has, for some time, encouraged countries endemic for schistosomiasis to control morbidity from this disease through mass drug administration (MDA) of the well-tolerated drug, praziquantel (PZQ). With the London Declaration in January 2012 and the promise by Merck Serono to eventually donate 250 million PZQ tablets per year, most endemic countries in sub-Saharan Africa have now developed national plans to do MDA for schistosomiasis morbidity control. More recently, based on two World Health Assembly (WHA) resolutions (WHA 54.19 & WHA 65.21) on schistosomiasis, countries are further encouraged to eliminate schistosomiasis, where feasible. The fight against schistosomiasis is therefore in a critical period of tremendous opportunities and equal challenges. How do we do the most effective job of MDA? What tools do we need to do this job better? How will we know when to move from morbidity control to elimination? What combinations of interventions, beyond MDA, are needed to eliminate transmission? The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has its Secretariat at the University of Georgia and with programs in more than 26 institutions in 19 countries it is trying to answer these very practical questions through multiple large field-based studies and the evaluation or development of better diagnostics for schistosomiasis. This presentation will summarize the current status of morbidity control and elimination programs and the operational research by SCORE that we hope will provide much-needed answers for national program managers so they can most effectively pursue these critical public health programs.

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Malaria is the one of major diseases which threatens people’s life in Africa. Out of humanitarianism, Chinese scientists has contributed to research of Artemisinin and ACTS more than 30 years, China provides long-term antimalaria assistance to Africa and gain great achievements. In Moheli, the island of Comoros, the antimalaria group used a new strategy which universal medication and proactive intervention. They established not only an effective antimalaria system and reporting system but also a local antimalaria team. Furthermore, they enhanced publicity and put mass protection and treatment into effect. Finally, they achieved significant result. In order to apply those successful experience to other countries in Africa, this paper summed up those experience and inspirations.

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Since infectious diseases heed no national borders, international research collaboration across borders must be enhanced. The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan launched the J-GRID program in the fiscal year (FY) 2005, which consists of the two elements; (1) the construction of collaboration centers in Asian and African countries on a reciprocal basis between a Japanese university/institution and an overseas partner university/institution and (2) the networking of those collaboration centers and setting up its headquarters at RIKEN. J-GRID initiated with 5 collaboration centers in 3 Asian countries has expanded to include 13 centers in 8 countries (6 in Asia and 2 in Africa). The aims of J-GRID include conducting high quality research on infectious diseases of regional and global importance, advancing relevant technologies and developing human resources in the field. In this way, J-GRID is expected to contribute to the public health of the host countries, Japan and the rest of the world. After the completion of the first start-up phase, Term I (2005–2009), J-GRID has stepped up its activity for the second step-up phase, Term II (2010–2014). While the first term was just like an incubation period, the second term should be the exponential growth phase, maximizing its research activities. Indeed, J-GRID is now generating remarkable research outcomes with an increasing number of publications. The mid-term evaluation made by the MEXT in FY2012 commended J-GRID as an ideal model to demonstrate Japan’s leadership, in science and technology, and strongly recommended its extension in years to come after Term II terminates in FY 2014.

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A population-based cohort study on pediatric infectious diseases was established at Khanh Hoa Province, central Vietnam in 2006, to determine the etiology and risk factors for severe pediatric infectious diseases (SPID) such as acute respiratory infection (ARI), diarrhea and dengue which are the major causes of under 5 mortality. A population census survey was conducted in Nha-Trang and Ninh-Hoa to collect demographic, social-behavioral data and disease burden on SPID. The study site covered a population of 353,525 residing in 75,826 households with 24,781 children less than 5 years. Hospital databases from two hospitals covering the region were obtained. Linking the census and hospital databases, we were able to investigate on a variety of SPID such as environmental tobacco smoking exposure and increased risked of pediatric pneumonia hospitalization, population density, water supply and risk of dengue fever and animal livestock and risk of hospitalized diarrhea. To determine incidence, viral etiology and risk factors for pediatric ARI/pneumonia, we setup a population based prospective hospitalized Pediatric ARI surveillance at Khanh Hoa General Hospital, Nha-Trang in February 2007. The study has revealed RSV, rhinovirus and influenza A as major viral pathogens, role of multiple viral infection and its interaction with bacteria in the development of pneumonia. In addition, we are also conducting a birth cohort study to investigate the incidence of congenital infection and its impact on physical-neurological development, and role of host genetic polymorphism on SPID hospitalization in Vietnam. Population mobility, high cost of regular census update and low mortality are the challenges.

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In The Gambia, West Africa, the prevalence of chronic hepatitis B virus (HBV) infection in adults exceeds eight percent and hepatocellular carcinoma (HCC) has been the most frequent type of malignancy. Two population-based intervention studies to control HBV infection, namely, GHIS (Gambia Hepatitis Intervention Study) and PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa), are discussed. The GHIS started in 1986 as a nation-wide trial of the HBV vaccine to evaluate the effectiveness of infant HBV vaccination in preventing HCC in adulthood. The vaccine was progressively introduced into the Expanded Program of Immunization (EPI) of The Gambia over four years in a phased manner, called the “stepped-wedge” design. This was because instantaneous universal vaccination in the country was impossible for logistic and financial reasons. However, this design also allowed the study to have an unvaccinated control group which consisted of the newborns of the areas where HBV vaccine has not yet been incorporated in the EPI. To assess the outcome, a national cancer registry was founded and all HCC patients in this birth cohort are linked with the vaccine trial database. The study is still ongoing to answer whether the HBV vaccine in infancy prevent HCC in adulthood in The Gambia. Although the universal HBV vaccination since 1990 has been successful in reducing the prevalence of chronic HBV infection in young Gambians, the number of HCC cases may not decline over the next decades as people infected prior to the immunization program are likely to continue to develop the diseases. To reduce the HCC incidence through community-based screening of HBV infection and provision of antiviral therapy, the PROLIFICA project started in 2011. Study hypothesis and design of these two studies, GHIS and PROLIFICA, are further discussed.

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This article is based on a talk given at the Japanese Society for Tropical medicine Annual Meeting in 2014. The severe febrile illness study was established in 2005. The aim of the project was to define the aetiology of febrile disease in children admitted to a hospital in Tanzania. Challenges arose in many areas: Study design: An initial plan to recruit only the severely ill was revised to enroll all febrile admissions leading to a more comprehensive dataset but much increased costs. Operationally a decision was made to set up a paediatric acute admissions unit (PAAU) in the hospital to facilitate recruitment and to provide appropriate initial care in line with perceived ethical obligations. This had knock on effects relating to the responsibilities that were taken on but also some unexpected positive outcomes. Study personnel: Local research staff were sometimes called upon to make up temporary shortfalls in the hospital staffing. Lack of staff made it impossible to recruit patients around the clock, seven days a week creating the challenge of ensuring representative sampling. Quality control: Studies based on clinical examination create unique quality control challenges—how to ensure that clinical staff are examining in a systematic and reproducible way. We designed a sub-study to both explore this and improve quality. Summary: Setting up clinical research projects is severely resource poor settings creates many challenges including those of an operational, technical and ethical nature. Whilst there are no ‘right answers’ an awareness of these problems can help overcome them.

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Emerging infectious diseases include newly identified diseases caused by previously unknown organisms or diseases found in new and expanding geographic areas. Viruses capable of causing clinical disease associated with fever and bleeding are referred to as viral hemorrhagic fevers (VHFs). Arenaviruses and Bunyaviruses, both belonging to families classified as VHFs are considered major etiologies of hemorrhagic fevers caused by emerging viruses; having significant clinical and public health impact. Because these viruses are categorized as Biosafety Level (BSL) 3 and 4 pathogens, restricting their use, biological studies including therapeutic drug and vaccine development have been impeded. Due to these restrictions and the difficulties in handling such live viruses, pseudotype viruses bearing envelope proteins of VHF viruses have been developed using vesicular stomatitis virus (VSV) as a surrogate system. Here, we report the successful developments of two pseudotype VSV systems; bearing the envelope proteins of Lujo virus and severe fever with thrombocytopenia syndrome (SFTS) virus, both recently identified viruses of the family Arenaviridae and Bunyaviridae, respectively. My presentation will summarize the characterization of the envelope proteins of Lujo virus including its cellular receptor use and cell entry mechanisms. In addition, I will also present a brief introduction of SFTS reported in Japan and the diagnostic studies in progress using these newly pseudotype VSV system.

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Streptococcus pneumoniae is a major worldwide cause of morbidity and mortality. Pneumococcal carriage is considered to be an important source of horizontal spread of this pathogen within the community. Pneumococcal conjugate vaccine (PCV) is capable of inducing serotype-specific antibodies in sera of infants, and has been suggested to reduce nasopharyngeal carriage of vaccine-type pneumococci in children. PCV is generally immunogenic for pediatric patients with invasive pneumococcal disease, with an exception for the infecting serotypes. Based on evidences from the clinical trials of PCV, the health impact of childhood pneumococcal pneumonia appears to be high in developing countries where most of global childhood pneumonia deaths occur. PCV vaccination may prevent hundreds of deaths per 100,000 children vaccinated in developing countries, while PCV vaccination is expected to prevent less than 10 deaths per 100,000 children vaccinated in the developed countries. Therefore, the WHO has proposed a strategy to reduce the incidence of severe pneumonia by 75% in child less than 5 years of age compared to 2010 levels by 2025.

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The currently available influenza vaccines were developed in the 1930s through the 1960s using technologies that were state-of-the art for the times. Decades of advancement in virology and immunology have provided the tools for making better vaccines against influenza virus.Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing.Otherwise, MF59 adjuvanted influenza vaccine, ATIV was well tolerated in healthy young children and elderly after each of 3 doses and induced greater, longer-lasting, and broader immune responses than a nonadjuvanted trivalent inactivated influenza vaccine, TIV. The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain. In case of AS03 ATIV, the safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza.A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.In conclusion, current improved influenza vaccines are; in the problem target groups are children aged 6–24 months and people over 65 years old of age. Only ATIV has shown significantly greater efficacy than TIV, and its safe.

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Although the tremendous effort has been paid by scientists for creating HIV vaccine over the past three decades since the discovery of HIV-1, the HIV vaccine development still has a long way to go. Only one HIV vaccine, RV144, has been proved to be moderately effective by the clinical trials, but there has been much debate about its usefulness. The difficulties of HIV vaccine development includes the attacks to host’s immune system by HIV and the emergence of various escape mutants. The necessity of large clinical trials for the proof of efficacy also makes HIV vaccine development difficult.One the other hand, Treatment as Prevention (TasP) or Preexposure Prophylaxis (PrEP) has revealed to be highly effective for HIV prevention.Those preventive strategies using antiretroviral therapy is one of the recent main stream of HIV policy worldwide.However, it is believed that a sustained end of the HIV pandemic is guaranteed by the combination of nonvaccine prevention and the development of a safe and effective HIV vaccine. The continuous efforts are needed for the HIV vaccine development.

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The Great East Japan Earthquake on March 11, 2011, besides further studying the appropriateness of the initial response and post-countermeasures against the severe Fukushima nuclear accident, has now increased the importance of the epidemiological study in comprehensive health risk management and radiation protection; lessons learnt from the Chernobyl accident should be also implemented. Therefore, since May 2011, Fukushima Prefecture has started the “Fukushima Health Management Survey Project” for the purpose of long-term health care administration and early diagnosis/treatment for the prefectural residents. Basic survey is under investigation on a retrospective estimation of external exposure of the first four months. As one of the four detailed surveys, the thyroid ultrasound examination has clarified the increased detection rate of childhood thyroid cancers as a screening effect in the past three years and so thyroid cancer occurrence by Fukushima nuclear power plant accident, especially due to radioactive iodine will be discussed despite of difficult challenge of accurate estimation of low dose and low-dose rate radiation exposures. Through the on-site valuable experience and a difficult challenge for recovery, we should learn the lessons from this severe and large-scale nuclear accident, especially how to countermeasure against public health emergency at the standpoint of health risk and also social risk management.

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This article summarizes observations made in Northern Uganda and a lecture given at the Nodding Syndrome Workshop in Nagasaki September 2013. The objective of the manuscript is to summarize the current knowledge on nodding syndrome and to provide an agenda for investigations into the epidemiology, pathophysiology, diagnosis and care management of nodding syndrome in Uganda.

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