Treatment and outcomes of high-risk neuroblastoma in Southeast Asia: a single-institution experience and review of the literature

INTRODUCTION@#In Europe and North America, the majority of children with high-risk neuroblastoma survive the disease. Elsewhere, the treatment outcomes are poor.@*METHODS@#A retrospective review of children treated for high-risk neuroblastoma in a single institution in Singapore from 2007 to 2019 was carried out. Treatment consisted of intensive chemotherapy, surgery aimed at gross total resection of residual disease after chemotherapy, consolidation with high-dose therapy followed by autologous stem cell rescue, and radiotherapy to the primary and metastatic sites followed by maintenance treatment with either cis-retinoic acid or anti-disialoganglioside monoclonal antibody therapy. Survival data were examined on certain clinical and laboratory factors.@*RESULTS@#There were 57 children (32 male) treated for high-risk neuroblastoma. Their mean age was 3.9 (range 0.7-14.9) years. The median follow-up time was 5.5 (range 1.8-13.0) years for the surviving patients. There were 31 survivors, with 27 patients surviving in first remission, and the five-year overall survival and event-free survival rates were 52.5% and 47.4%, respectively. On log-rank testing, only the group of 17 patients who were exclusively treated at our centre had a survival advantage. Their five-year overall survival rate compared to patients whose initial chemotherapy was done elsewhere was 81.6% versus 41.1% (P = 0.011), and that of event-free survival was 69.7% versus 36.1% (P = 0.032). Published treatment results were obtained from four countries in Southeast Asia with five-year overall survival rates from 13.5% to 28.2%.@*CONCLUSION@#Intensified medical and surgical treatment for high-risk neuroblastoma proved to be effective, with superior survival rates compared to previous data from Southeast Asia.

Ebola virus disease: Getting to know a new emerging foe.

Viral hemorrhagic fevers have been at the top of the severity scale in terms of morbidity and mortality among human beings. Many of the viruses have their reservoirs in animal kingdom and from time to time they get introduced to humans and cause sporadic outbreaks and epidemics. Thousands of people from the Western African region have already succumbed to the complications due to Ebola virus infection.</p> <p>The South East Asian region including India has been affected by several outbreaks of communicable diseases like SARS, bird flu, swine flu etc. The current outbreak has been a global concern due to its spread beyond the African continent. WHO has declared EVD as an international health emergency and worldwide efforts have been enhanced to escalate research to find a vaccine or cure for the disease.

Tobacco use, exposure to second-hand smoke, and cessation training among the third-year medical and dental students in selected Member States of South-East Asia region: A trend analysis on data from the Global Health Professions Student Survey, 2005-2011.

Background: The Medical and Dental Global Health Professions Student Surveys (GHPSS) are surveys based in schools that collect self-administered data from students on the prevalence of tobacco use, exposure to second-hand smoke, and tobacco cessation training, among the third-year medical and dental students. Materials and Methods: Two rounds of medical and dental GHPSS have been conducted in Bangladesh, India, Myanmar, Nepal, Sri Lanka, and Thailand, among the third-year medical and dental students, between 2005 and 2006 and 2009 and 2011. Results: The prevalence of any tobacco use among third-year male and female medical students did not change in Bangladesh, India, and Nepal between 2005 and 2006 and 2009 and 2011; however, it reduced significantly among females in Myanmar (3.3% in 2006 to 1.8% in 2009) and in Sri Lanka (2.5% in 2006 to 0.6% in 2011). The prevalence of any tobacco use among third-year male dental students did not change in Bangladesh, India, Nepal, and Thailand between 2005 and 2006 and 2009 and 2011; however, in Myanmar, the prevalence increased significantly (35.6% in 2006 to 49.5% in 2009). Among the third-year female students, a significant increase in prevalence was noticed in Bangladesh (4.0% in 2005 to 22.2% in 2009) and Thailand (0.7% in 2006 to 2.1% in 2011). It remained unchanged in the other three countries. Prevalence of exposure to second-hand smoke (SHS) both at home and in public places, among medical students, decreased significantly in Myanmar and Sri Lanka between 2006 and 2009 and in 2011. Among dental students, the prevalence of SHS exposure at home reduced significantly in Bangladesh, India, and Myanmar, and in public places in India. However, there was an increase of SHS exposure among dental students in Nepal, both at home and in public places, between 2005 and 2011. Medical students in Myanmar, Nepal, and Sri Lanka reported a declining trend in schools, with a smoking ban policy in place, between 2005 and 2006 and 2009 and 2011, while proportions of dental students reported that schools with a smoking ban policy have increased significantly in Bangladesh and Myanmar. Ever receiving cessation training increased significantly among medical students in Sri Lanka only, whereas, among dental students, it increased in India, Nepal, and Thailand. Conclusion: Trends of tobacco use and exposure to SHS among medical and dental students in most countries of the South-East Asia Region had changed only relatively between the two rounds of GHPSS (2005-2006 and 2009-2011). No significant improvement was observed in the trend in schools with a policy banning smoking in school buildings and clinics. Almost all countries in the SEA Region that participated in GHPSS showed no significant change in ever having received formal training on tobacco cessation among medical and dental students.

Prevalence of smokeless tobacco use among adults in WHO South-East Asia.

Smokeless tobacco (SLT) use is an understudied problem in South-East Asia. Information on SLT use among the adult population was collected from various available sources. SLT use prevalence varies among countries in the region. The prevalence of SLT use is known for all countries at national level in the region with the exception of Bhutan and DPR Korea. For Bhutan, data pertains to Thimphu only. There is no available data on SLT use for DPR Korea. Using all available data from Bhutan, India, Myanmar, Nepal, and Sri Lanka, SLT use was found to be higher among males as compared to females; however, in Bangladesh, Indonesia, and Thailand, SLT use was higher among females as compared to males. Among males, prevalence of SLT use varied from 51.4% in Myanmar to 1.1% in Thailand. Among females, the prevalence of SLT use varied from 27.9% in Bangladesh to 1.9% in Timor-Leste. The prevalence also varies in different parts of countries. For instance, the prevalence of current use of SLT in India ranges from 48.7% in Bihar to 4.5% in Himachal Pradesh. In Thailand, prevalence of current use of tobacco use varies from 0.8% in Bangkok to over 4% in the northern (4.1%) and northeastern (4.7%) region. Among all SLT products, betel quid was the most commonly used product in most countries including Bangladesh (24.3%) and Thailand (1.8%). However, Khaini (11.6%) chewing was practiced most commonly in India. Nearly 5% of the adult population used tobacco as dentifrice in Bangladesh and India. SLT is more commonly used in rural areas and among disadvantaged groups. Questions from standard "Tobacco Questions for Surveys (TQS)" need to be integrated in routine health system surveys in respective countries to obtain standardized tobacco use data at regular intervals that will help in providing trends of SLT use in countries.

Pneumonia in South-East Asia Region: Public health perspective.

Globally, pneumonia is the leading cause of death in young children and burden of disease is disproportionately high in South-East Asia Region of WHO. This review article presents the current status of pneumonia disease burden, risk factors and the ability of health infrastructure to deal with the situation. Literature survey was done for the last 20 years and data from country offices were also collected. The estimated incidence of pneumonia in under five children is 0.36 episodes per child, per year. Risk factors are malnutrition (40% in India), Indoor air pollution, non-breast feeding, chronic obstructive pulmonary disease, etc. Strengthening of health care delivery system for early detection and treatment and as well as minimization of preventable risk factors can avert a large proportion of death due to pneumonia.

Haemoglobinopathies in Southeast Asia.

In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to over 60 different thalassaemia syndromes, making Southeast Asia the locality with the most complex thalassaemia genotypes. The four major thalassaemic diseases are Hb Bart's hydrops fetalis (homozygous α-thalassaemia 1), homozygous β-thalassaemia, β-thalassaemia/Hb E and Hb H diseases. α-Thalassaemia, most often, occurs from gene deletions whereas point mutations and small deletions or insertions in the β-globin gene sequence are the major molecular defects responsible for most β-thalassaemias. Clinical manifestations of α-thalassaemia range from asymptomatic cases with normal findings to the totally lethal Hb Bart's hydrops fetalis syndrome. Homozygosity of β-thalassaemia results in a severe thalassaemic disease while the patients with compound heterozygosity, β-thalassaemia/Hb E, present variable severity of anaemia, and some can be as severe as homozygous β-thalassaemia. Concomitant inheritance of α-thalassaemia and increased production of Hb F are responsible for mild clinical phenotypes in some patients. However, there are still some unknown factors that can modulate disease severity in both α- and β-thalassaemias. Therefore, it is possible to set a strategy for prevention and control of thalassaemia, which includes population screening for heterozygotes, genetic counselling and foetal diagnosis with selective abortion of affected pregnancies.

Non-communicable diseases in the South-East Asia Region: Burden, strategies and opportunities.

Non-communicable diseases (NCDs) are a global health and developmental emergency, as they cause premature deaths, exacerbate poverty and threaten national economies. In 2008, they were the top killers in the South-East Asia region, causing 7.9 million deaths; the number of deaths is expected to increase by 21% over the next decade. One-third of the 7.9 million deaths (34%) occurred in those <60 years of age (compared to 23% in the rest of the world). Of the total deaths in the South-East Asia region (14.5 million), cardiovascular diseases accounted for 25%, chronic respiratory diseases 9.6%, cancer 7.8% and diabetes 2.1%. NCDs are largely attributable to a few preventable risk factors, all of which are highly prevalent in the region—tobacco use, unhealthy diet, lack of physical activity and harmful use of alcohol. Key strategies for the prevention and control of NCDs include (i) reducing exposure to risk factors through health promotion and primary prevention, (ii) early diagnosis and management of people with NCDs, and (iii) surveillance to monitor trends in risk factors and diseases. Tackling NCDs calls for a paradigm shift: from addressing each NCD separately to collectively addressing a cluster of diseases in an integrated manner, and from using a biomedical approach to a public health approach guided by the principles of universal access and social justice. High levels of commitment and multisectoral actions are needed to reverse the growing burden of NCDs in the South-East Asia region.

Clinical Characteristics and Etiology of Travelers' Diarrhea among Korean Travelers Visiting South-East Asia

The morbidity of travelers' diarrhea (TD) is still high. This study examined the incidence of common pathogens and characteristics of TD among Korean travelers who visited South-East Asian countries. We performed a prospective study involving 479 Korean travelers with diarrheal disease from February 2009 to April 2009 and stool samples were examined and questionnaire surveys were done after arrival. Enterotoxigenic Escherichia coli (ETEC) was found in 36.0% of TD cases, as were the following: Enteroaggregative Escherichia coli (EAEC) in 27.0%, Vibrio parahaemolyticus in 13.1%, and Norovirus in 11.5%. The detected rate of classic TD was higher in men (P = 0.007), in patients who had a shorter duration trip (P = 0.023) and in patients who drank more than 1 liter of water per day (P = 0.037). Positive stool culture rates were higher in men (P = 0.005), in hospitalized patients (P = 0.013). and in those who consumed impure water or raw foods (P = 0.033). A higher severity of disease corresponded to a significantly higher culture positivity rate (P = 0.029). We should consider the possibility of other pathogens in addition to ETEC in patients with TD who visit South-East Asia. Travelers need to educate about risk factors associated with TD.

Dengue in Southeast Asia: epidemiological characteristics and strategic challenges in disease prevention / Dengue no Sudeste Asiático: características epidemiológicas e desafios estratégicos na prevenção da doença

Dengue emerged as a public health burden in Southeast Asia during and following the Second World War and has become increasingly important, with progressively longer and more frequent cyclical epidemics of dengue fever/dengue hemorrhagic fever. Despite this trend, surveillance for this vector-borne viral disease remains largely passive in most Southeast Asian countries, without adequate laboratory support. We review here the factors that may have contributed to the changing epidemiology of dengue in Southeast Asia as well as challenges of disease prevention. We also discuss a regional approach to active dengue virus surveillance, focusing on urban areas where the viruses are maintained, which may be a solution to limited financial resources since most of the countries in the region have developing economies. A regional approach would also result in a greater likelihood of success in disease prevention since the large volume of human travel is a major factor contributing to the geographical spread of dengue viruses.

A dengue emergiu como problema de saúde pública no Sudeste Asiático durante e após a Segunda Guerra Mundial, e vem se agravando cada vez mais, com epidemias cíclicas progressivamente mais longas e freqüentes de dengue e de febre hemorrágica da dengue. Apesar dessa tendência, a vigilância dessa virose transmitida por vetores permanece basicamente passiva na maioria dos países do Sudeste Asiático, sem apoio laboratorial adequado. O artigo apresenta uma revisão dos fatores que podem ter contribuído para a mudança no perfil epidemiológico da dengue na região, além de discutir os desafios para a prevenção da doença. Analisa-se também uma abordagem regional para a vigilância ativa dos vírus da dengue, focando as áreas urbanas onde eles se mantêm, o que pode representar uma solução à limitação de recursos financeiros, uma vez que a maioria dos países da região tem economias em desenvolvimento. Uma abordagem regional também resultaria em maior probabilidade de sucesso na prevenção da doença, já que a grande circulação de viajantes na região é um fator importante na disseminação dos vírus da dengue.

Modeling the Dynamics and Control of Transmission of Schistosoma japonicum and S. mekongi in Southeast Asia

A mathematical model for transmission of schistosomes is useful to predict effects of various control measures on suppression of these parasites. This review focuses on epidemiological and environmental factors in Schistosoma japonicum and Schistosoma mekongi infections and recent advances in mathematical models of Schistosoma transmission.

Foodborne Intestinal Flukes in Southeast Asia

In Southeast Asia, a total of 59 species of foodborne intestinal flukes have been known to occur in humans. The largest group is the family Heterophyidae, which constitutes 22 species belonging to 9 genera (Centrocestus, Haplorchis, Heterophyes, Heterophyopsis, Metagonimus, Procerovum, Pygidiopsis, Stellantchasmus, and Stictodora). The next is the family Echinostomatidae, which includes 20 species in 8 genera (Artyfechinostomum, Acanthoparyphium, Echinochasmus, Echinoparyphium, Echinostoma, Episthmium, Euparyphium, and Hypoderaeum). The family Plagiorchiidae follows the next containing 5 species in 1 genus (Plagiorchis). The family Lecithodendriidae includes 3 species in 2 genera (Phaneropsolus and Prosthodendrium). In 9 other families, 1 species in 1 genus each is involved; Cathaemaciidae (Cathaemacia), Fasciolidae (Fasciolopsis), Gastrodiscidae (Gastrodiscoides), Gymnophallidae (Gymnophalloides), Microphallidae (Spelotrema), Neodiplostomidae (Neodiplostomum), Paramphistomatidae (Fischoederius), Psilostomidae (Psilorchis), and Strigeidae (Cotylurus). Various types of foods are sources of human infections. They include freshwater fish, brackish water fish, fresh water snails, brackish water snails (including the oyster), amphibians, terrestrial snakes, aquatic insects, and aquatic plants. The reservoir hosts include various species of mammals or birds.The host-parasite relationships have been studied in Metagonimus yokogawai, Echinostoma hortense, Fasciolopsis buski, Neodiplostomum seoulense, and Gymnophalloides seoi; however, the pathogenicity of each parasite species and host mucosal defense mechanisms are yet poorly understood. Clinical aspects of each parasite infection need more clarification. Differential diagnosis by fecal examination is difficult because of morphological similarity of eggs. Praziquantel is effective for most intestinal fluke infections. Continued efforts to understand epidemiological significance of intestinal fluke infections, with detection of further human cases, are required.

Lessons learned about opportunistic infections in southeast Asia.

Southeast Asia is a region where the number of people infected with HIV/AIDS is one of the fastest growing in the world. Tuberculosis (TB) has grown along with the HIV epidemic. TB is not only the most common AIDS-defining illness but is also the leading cause of morbidity and mortality in AIDS patients. Cryptococcosis (meningitis or disseminated) is one of the most common opportunistic infections in AIDS patients. Cryptococcal meningitis is the first in the differential diagnosis considered with meningeal irritation. Penicillosis, a unique systemic mycosis, is an important emerging public health problem and has been classified as an AIDS defining illness in endemic areas like Thailand. Pneumocystis carinii (jiroveci) pneumonia has been one of the most important opportunistic infections in AIDS patients. Among parasitic infections, cryptosporidiosis is the most common intestinal protozoan infection relating to diarrhea in AIDS patients and toxoplasmosis is the only parasitic infection of the nervous system with a substantial incidence, up to 14.8%. Cytomegalovirus (CMV) retinitis has a lower prevalence compared to other opportunistic infections. In the era of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections has significantly reduced in the past few years. Subsequently, the phenomena of immune restoration inflammatory syndrome (IRIS) in AIDS patients has been reported in this region as a result of HAART.

Genetic disorders and malaria in Indo-China region.

High prevalence of malaria in Southeast Asia including Thailand is believed to be a major public health problem to the population in this area since time immemorial. Adaptation of the population in this area following the principle of natural selection coupled with genetic disorders can be expected. Some good examples for natural selection of malaria are the co-existence of high prevalence of thalassaemia as well as glucose-6-phosphate dehydrogenase deficiency. In this report, general aspects of some important genetic disorders and malaria in Indo-China area (Thailand, Laos, Cambodia, Myanmar, Vietnam, Yunnan and Manipur) are summarized and discussed.

Can Southeast Asia eradicate yaws by 2010? Some lessons from the Yaws Eradication Programme of India.

Yaws has traditionally been known as a skin disease that affects people living in hilly, remote and inaccessible areas. Despite the availability of successful treatment and yaws control programmes worldwide since 1948, yaws is endemic in a number of countries, probably because it is not considered a priority disease for eradication. The presence of a disease that can be eradicated in a community can be taken as a sign of 'backwardness' and an indicator of inappropriate public health efforts. Yaws is endemic in 3 countries of the Southeast Asia (SEA) Region of WHO-indonesia, India and Timor-Leste. The WHO SEA Regional Office has set a target for yaws eradication from the region by year 2010. Yaws eradication is at various stages in these countries. India has reported no cases for the past 3 years and has declared elimination. In the other 2 countries yaws eradication programmes are in their infancy and achieving the WHO regional goal appears impossible. However, if lessons are learnt from the Yaws Eradication Programme in India and an externally funded, technically supported, vertical programme is started immediately in Indonesia and Timor-Leste, the target would not be difficult to accomplish.

Dengue in the Americas and Southeast Asia: do they differ?

The populations of Southeast Asia (SE Asia) and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF), principally in children, whereas in the Americas there were 2.8 million dengue fever (DF) cases, principally in adults, and only 65 000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.

Las poblaciones de Asia suroriental y de la América tropical son similares y los cuatro tipos de virus del dengue de origen asiático son endémicos en ambas regiones. Aun así, durante períodos quinquenales comparables ocurrieron 1,16 millones de casos de dengue hemorrágico (DH) en Asia suroriental, principalmente en niños, mientras que en las Américas ocurrieron 2,8 millones de casos de dengue, principalmente en adultos, y solo 65 000 casos de DH. El objetivo de esta revisión es explicar estas diferencias regionales. En el sudeste asiático, con la Segunda Guerra Mundial se extendieron las poblaciones del mosquito Aedes aegypti y se diseminó el virus del dengue. En las Américas, los esfuerzos para erradicar el A. aegypti en las décadas de 1940 y 1950 restringieron las epidemias de dengue principalmente a la cuenca del Caribe. Cuba escapó a las infecciones por el genotipo americano del dengue-2 y un endémico asiático del dengue-3 en las décadas de 1960 y 1970. Infecciones sucesivas con el virus del dengue-1 y un genotipo asiático del dengue-2 dio como resultado una epidemia de DH en 1981. Cuando este virus del dengue-2 se introdujo en otros países caribeños encontró poblaciones con un alto grado de inmunidad al genotipo americano del dengue-2. Durante las décadas de 1980 y 1990, la rápida expansión de las poblaciones de A. aegyti en Brasil favorecieron la aparición de epidemias sucesivas de dengue-1, dengue-2 y dengue-3. Estas, no obstante, provocaron principalmente casos de dengue con sorpresivamente pocos casos de DH. La ausencia de altas tasas de formas graves de dengue en Brasil y otros países de la Región puede explicarse en parte por la amplia presencia de genes humanos de resistencia al dengue. La comprensión de la naturaleza y de la distribución de estos genes crea grandes expectativas para frenar las formas graves de dengue. Las investigaciones futuras sobre la infección por los virus del dengue deben poner énfasis en diseños basados...

Working towards TB elimination the WHO Regional Strategic Plan (2006-2015).

DOTS has expanded rapidly in the South-East Asia Region over the period of the Partnership's first Global Plan (2001-2005), with almost 100% geographical coverage achieved in 2005. All countries have made impressive progress in improving coverage and quality. This progress has been made possible through strong political commitment and large investments in TB control for improved infrastructure, reliable drug supply, increased staffing, improved laboratory services, and intensified training and supervision. Accomplishing the objectives outlined in this document will require sustaining the progress in all countries and particularly in the five high burden countries for achieving major regional and global impact. National TB programmes will need to be supported to maintain or surpass the 70% case detection and 85% treatment success rates. The achievement of the TB-related targets linked to the MDGs will also depend on how effectively initiatives such as DOTS-Plus, PPM DOTS and interventions for TB/ HIV among others, are implemented. National governments and development partners must fulfill their commitments to mobilizing and sustaining adequate resources to support the full range of activities envisaged. The benefits of full and effective implementation of all the planned interventions would be substantial. These will result in 20 to 25 million TB cases being treated in DOTS program mes and more than 150 000 drug-resistant cases receiving treatment through DOTS-Plus during the period 2006-2015. In addition, at least 250 000 HIV-infected TB patients may also receive anti-retroviral therapy. As a consequence, the prevalence of TB is expected to fall below 175/100 000 and the number of TB deaths is expected to fall to between 100 000 and 150 000 per year. There would also be substantial economic benefits given that TB disproportionately affects adults in their most productive years. Considering these aspects, it is expected that the TB incidence will decline significantly during this period so that the Millennium Development Goals would be met by or ahead of 2015.