Rabies control in South and Southeast Asia

We have the knowledge and tools to eliminate the threat of canine rabies but this disease, nevertheless, remains a public health threat in many parts of the world. Lack of motivation by governments, cultural issues and inadequate funding remain barriers. This is amazing since the number of human rabies deaths worldwide is greater than that from polio, meningococcal meningitis, Japanese encephalitis, yellow fever, SARS, bird flue and other scourges that attract more attention. Safe and effective vaccines are now widely available. Reduced dose effective and less expensive post-exposure vaccination regimens have helped eliminate nerve tissue vaccines in Thailand, Philippines and Sri Lanka. India and Pakistan, the major users of dangerous nerve tissue derived Semple type vaccine, are now considering following suite. Immediate wound care and prompt use of a potent vaccine will save a majority of infected persons. Rabies immunoglobulin, injected into and around bite wounds, provides added safety for the severely exposed. The high cost of rabies immunoglobulin and tissue culture vaccines are remaining barriers, but new manufacturers and the use of intradermal vaccination schedules can reduce costs. Ultimately, it is the need to control rabies in dogs that must occupy most of our attention. The tools are available, but attitudes must change before they can be applied. There have been many new developments since publication of the last WHO rabies expert committee report in 1992 (new version in print)] and we will address those that have practical applicability.     

The evolutionary biology of endometriosis

We provide the first analysis and synthesis of the evolutionary and mechanistic bases for risk of endometriosis in humans, structured around Niko Tinbergen''s four questions about phenotypes: phylogenetic history, development, mechanism and adaptive significance. Endometriosis, which is characterized by the proliferation of endometrial tissue outside of the uterus, has its phylogenetic roots in the evolution of three causally linked traits: (1) highly invasive placentation, (2) spontaneous rather than implantation-driven endometrial decidualization and (3) frequent extensive estrogen-driven endometrial proliferation and inflammation, followed by heavy menstrual bleeding. Endometriosis is potentiated by these traits and appears to be driven, proximately, by relatively low levels of prenatal and postnatal testosterone. Testosterone affects the developing hypothalamic–pituitary–ovarian (HPO) axis, and at low levels, it can result in an altered trajectory of reproductive and physiological phenotypes that in extreme cases can mediate the symptoms of endometriosis. Polycystic ovary syndrome, by contrast, is known from previous work to be caused primarily by high prenatal and postnatal testosterone, and it demonstrates a set of phenotypes opposite to those found in endometriosis. The hypothesis that endometriosis risk is driven by low prenatal testosterone, and involves extreme expression of some reproductive phenotypes, is supported by a suite of evidence from genetics, development, endocrinology, morphology and life history. The hypothesis also provides insights into why these two diametric, fitness-reducing disorders are maintained at such high frequencies in human populations. Finally, the hypotheses described and evaluated here lead to numerous testable predictions and have direct implications for the treatment and study of endometriosis. Lay summary: Endometriosis is caused by endometrial tissue outside of the uterus. We explain why and how humans are vulnerable to this disease, and new perspectives on understanding and treating it. Endometriosis shows evidence of being caused in part by relatively low testosterone during fetal development, that ‘programs’ female reproductive development. By contrast, polycystic ovary syndrome is associated with relatively high testosterone in prenatal development. These two disorders can thus be seen as ‘opposite’ to one another in their major causes and correlates. Important new insights regarding diagnosis, study and treatment of endometriosis follow from these considerations.     

The evolutionary biology of poxviruses

The poxviruses (family Poxviridae) are a family of double-stranded viruses including several species that infect humans and their domestic animals, most notably Variola virus (VARV), the causative agent of smallpox. The evolutionary biology of these viruses poses numerous questions, for which we have only partial answers at present. Here we review evidence regarding the origin of poxviruses, the frequency of host transfer in poxvirus history, horizontal transfer of host genes to poxviruses, and the population processes accounting for patterns of nucleotide sequence polymorphism.     

The evolutionary origins of Southeast Asian Ovalocytosis

Southeast Asian Ovalocytosis (SAO) is a common red blood cell disorder that is maintained as a balanced polymorphism in human populations. In individuals heterozygous for the SAO-causing mutation there are minimal detrimental effects and well-documented protection from severe malaria caused by Plasmodium vivax and Plasmodium falciparum; however, the SAO-causing mutation is fully lethal in utero when homozygous. The present-day high frequency of SAO in Island Southeast Asia indicates the trait is maintained by strong heterozygote advantage. Our study elucidates the evolutionary origin of SAO by characterizing DNA sequence variation in a 9.5 kilobase region surrounding the causal mutation in the SLC4A1 gene. We find substantial haplotype diversity among SAO chromosomes and estimate the age of the trait to be approximately 10,005 years (95% CI: 4930–23,200 years). This date is far older than any other human malaria-resistance trait examined previously in Southeast Asia, and considerably pre-dates the widespread adoption of agriculture associated with the spread of speakers of Austronesian languages some 4000 years ago. Using a genealogy-based method we find no evidence of historical positive selection acting on SAO (s = 0.0, 95% CI: 0.0–0.03), in sharp contrast to the strong present-day selection coefficient (e.g., 0.09) estimated from the frequency of this recessively lethal trait. This discrepancy may be due to a recent increase in malaria-driven selection pressure following the spread of agriculture, with SAO targeted as a standing variant by positive selection in malarial populations.     

The role of research in international tobacco control

The future of the tobacco-produced disease epidemic rests in low- and middle-income countries, where cigarette sales are growing-the result of rising incomes, trade liberalization, liberalization of the treatment of women, and the introduction of Western-style advertising.Research on disease causation, epidemiology, and educational and policy interventions has contributed significantly to reducing smoking rates in developed countries. A similar contribution is needed in less affluent nations, but severe challenges are involved in implementing a robust research program in such countries.In an attempt to understand these challenges and begin to conceptualize an approach to overcoming them, I examine the need for and methods to achieve a program of meaningful research on tobacco and health, as well as health policy, in the developing world.     

Tobacco control and gender in Southeast Asia. Part I: Malaysia and the Philippines

In the World Health Organization's Western Pacific Region, being born male is the single greatest risk marker for tobacco use. While the literature demonstrates that risks associated with tobacco use may vary according to sex, gender refers to the socially determined roles and responsibilities of men and women, who initiate, continue and quit using tobacco for complex and often different reasons. Cigarette advertising frequently appeals to gender roles. Yet tobacco control policy tends to be gender-blind. Using a broad gender-sensitivity framework, this contradiction is explored in four Western Pacific countries. Part I of the study discusses issues surrounding gender and tobacco, and analyses developments in Malaysia and the Philippines. Part II deals with Singapore and Vietnam. In all four countries, gender was salient for the initiation and maintenance of smoking, and in Malaysia and the Philippines was highly significant in cigarette promotion. Yet, with a few exceptions, gender was largely unrecognized in control policy. Suggestions for overcoming this weakness in order to enhance tobacco control are made in Part II.     

The role of training in global tobacco control research

Despite the pandemic nature of the tobacco control problem, little attention has been given to the role of research training in stemming the global tide of tobacco use. Tobacco research plays a critical role in both shaping policy and saving lives, and training new tobacco researchers is an important part of the tobacco control agenda.There are several conceptual training models, all of which emphasize communicative partnerships and multidisciplinary approaches. It also is important to take cultural background and specificity into account when shaping research and training agendas.We present a number of successful training initiatives and address both the strengths and the pitfalls of these endeavors.     

Developmental plasticity and evolutionary biology

Fetal experience determines some of the characteristics of human adults. Well-nourished mothers have offspring who are adapted to affluent conditions; mothers on a low level of nutrition have offspring who are adapted to lean environments. If the mother's forecast of her offspring's future environment is incorrect, the health of her offspring may suffer severely. The developmental plasticity that accounts for the ill health of humans who are living in conditions of rapid economic change is commonplace in biology. Understanding the evolutionary background sets the developmental origins of ill health in humans in context and has profound implications for public health.     

Nutrition and socio-economic development in Southeast Asia.

While most Third World countries, particularly in Africa and Latin America, have experienced a deterioration in child welfare as a result of the severe economic downturn in the 1980s, Southeast Asia in general managed to sustain improvements in the situation of its children because it has maintained satisfactory rates of economic growth. However, there were exceptions within Southeast Asia. The Philippines, Vietnam, Dem. Kampuchea and Laos had unsatisfactory growth rates and, consequently, unsustained nutritional gains from the 1970s through the 1980s. Economic factors exerted a big impact on the Philippine nutrition situation, particularly on the dietary status of the households and the nutritional status of children. As a result of the economic dislocation occurring in the country, the nutritional gains of 1978-82 were not maintained in succeeding years. Unlike the case of Thailand, it has been estimated that the solution to nutritional problems in the Philippines is far from being achieved in the immediate future (Villavieja et al. 1989). On the other hand, the nutrition improvements in Thailand have been as remarkable as the economic growth over the last decade. Long-term investments in health, nutrition and other social services in Thailand (as well as in Indonesia) have paid off according to the assessment by the United Nations (1990). It appears, therefore, that the nutrition situation in developing countries is highly dependent on the economic situation, globally and nationally (Cornia et al. 1987), as well as on investment in social services. Adjustment policies should, therefore, consider their implications on distribution and poverty in order that they could positively contribute to the improvement of the nutrition of the people.     

Recommended dietary allowances harmonization in Southeast Asia

Issues and opportunities for RDA harmonization within the SEA region were first raised during the First Regional Forum and Workshop "RDAs: Scientific Basis and Future Directions", held in Singapore in March 1997. A regional review on RDAs in SEA showed general similarities for the different RDAs, although in some cases a country listed an exceptionally high or low RDA for a particular nutrient for a specific group. It also revealed differences in physiologic groupings and reference body weights, nutrients included and units of expression. Realizing these differences in RDA components between countries which makes technical composition different, a consensus on the need for regional collaboration and harmonization of RDAs was reached by participants from Indonesia, Malaysia, Philippines, Singapore, Thailand and Vietnam. A follow-up workshop was organized to work towards agreement throughout the region on common approaches, concepts and terminologies; application and uses, format and a research agenda. Round table discussions were held to arrive at specific recommendations for achieving harmonization. While divergence in opinions were expected, some clear-cut agreements were settled. Globalization envisions to achieve economic growth and development, with the effects expected to ripple through health, nutrition and welfare improvements. The harmonization of RDAs in SEA seeks to reach this vision by strengthening R and D capabilities (both logistic and manpower) within the region and within the countries in the region, as well as harmonizing the efforts of governments and industry within the region to reduce potential trade barriers such as those relating to food and nutrition quality assurance standards.     

罕见病患者权利的缺失与保护

新生儿筛查和患者登记系统是罕见病疾病管理的基础,本研究介绍国际新生儿筛查和罕见病患者登记现状,总结其特点,为进一步完善和促进中国罕见病疾病管理提供信息支持和借鉴参考。     

International consultation and the homogenization of psychiatry in Southeast Asia

The nature of psychiatric care varies little among the capital cities of Southeast Asia. Differences that may exist are of degrees along a common dimension. Colonial forces from the past and contemporary diffusion of modern psychiatry have produced this remarkably uniform pattern of thought and treatment across divergent national and cultural boundaries. Our paper analyzes the homogenization of psychiatry in Southeast Asia in three ways. First, we examine international mental health education, consultation and collaboration as interlocking mechanisms for the transfer of psychiatric technology. Second, the indirect and undesirable consequences of the diffusion of psychiatric knowledge and practice are analyzed. Third, we pose recommendations for countering these unanticipated consequences through evaluation research, ethical guidelines, and educational and intervention practices that strengthen indigenous healing resources.