Diseases In Southeast Asia Research Articles

Sera of patients with systemic lupus erythematosus cross-neutralizes dengue viruses.

Dengue is the most prevalent mosquito-borne disease in Southeast Asia, where the incidence of systemic lupus erythematosus (SLE) is approximately 30 to 53 per 100,000. Severe dengue, however, is rarely reported among individuals with SLE. Here, whether sera of patients with SLE cross-neutralize dengue virus (DENV) was investigated. Serum samples were obtained from individuals with SLE who were dengue IgG and IgM serology negative. Neutralization assays were performed against the three major DENV serotypes. Of the dengue serology negative sera of individuals with SLE, 60%, 61% and 52% of the sera at 1/320 dilution showed more than 50% inhibition against dengue type-1 virus (DENV-1), DENV-2 and DENV-3, respectively. The neutralizing capacity of the sera was significantly greater against DENV-1 (P < 0.001) and DENV-3 (P < 0.01) than against DENV-2 (P < 0.05). Neutralization against the DENV correlated with dengue-specific IgG serum titers below the cut-off point for dengue positivity. Depletion of total IgG from the sera of patients with SLE resulted in significant decreases of up to 80% in DENV inhibition, suggesting that IgG plays an important role. However, some of the SLE sera was still able to neutralize DENV, even with IgG titers <0.1 OD absorbance. Our findings suggest that sera of patients with SLE contain IgG, and possibly other type of antibodies, that can cross-neutralize DENV, which may explain the rarity of severe dengue in individuals with SLE. Further studies, are needed to further substantiate this finding and to elucidate the specific neutralizing epitopes recognized by the sera of individuals with SLE.

PHP92 - The Growth of Cost-Effectiveness Analyses in Asia

This study describes the cost-effectiveness analyses (CEA) literature for health interventions in Asian countries and identifies disease areas for which the number of CEA studies either exceeds or is less than the number expected given the disease’s population burden. We analyzed Tufts Medical Center’s CEA Registry, containing English-language cost-per-quality-adjusted life year (QALY) studies, and the Global Health CEA Registry, containing cost-per-disability-adjusted life year (DALY) averted studies, across four regions in Asia (defined by the World Health Organization’s Global Burden of Disease study): (1) South Asia; (2) Southeast Asia; (3) East Asia; and (4) High-Income Asia Pacific. For each region and disease area, we determined the number of published CEAs and the corresponding disease burden. Using ordinary least squares regression of publication count against disease burden in each region, we identified disease areas that are relatively “over”- or “under”-studied within that region compared to other conditions. We identified 613 CEAs in the four regions, including 243 for East Asia, 180 for Southeast Asia, 130 for South Asia, and 200 for High-Income Asia Pacific (not mutually exclusive). Publication grew rapidly, from one study in 1996 to 114 studies in 2016. Neoplasms were the most studied disease category in East Asia (n=60) and High-Income Asia Pacific (n=44), while diarrheal diseases were the most studied disease category in South Asia (n=25) and Southeast Asia (n=30). Non-communicable diseases in East Asia, and cardiovascular disease in Southeast Asia and High-Income Asia Pacific were under-studied relative to their disease burden. Neoplasms in East Asia were relatively over-studied, as were HIV and tuberculosis in South Asia. Publication of CEAs for Asian countries is growing rapidly. There are opportunities to focus future research on disease areas that have received less attention than apparently warranted by their population burden.

ITRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma

ABSTRACTNasopharyngeal carcinoma (NPC) is a highly prevalent disease in Southeast Asia. The disease is typically diagnosed in the later stages, and chemotherapy resistance often causes treatment failure. To investigate the underlying mechanisms of drug resistance, we searched for chemoresistant-associated proteins in NPC and drug-resistant NPC cell lines using isobaric tags for relative and absolute quantitation combined with nano liquid chromatography-tandem mass spectrometry. The chemoresistant NPC cell lines CNE1DDP and CNE2DDP were resistant to 1 mg/L cisplatin, had resistant indexes of 4.58 and 2.63, respectively, and clearly grew more slowly than the NPC cell lines CNE1 and CNE2. Using three technical replicates, we identified 690 nonredundant proteins, 56 of which were differentially expressed in both groups of cell lines (CNE1 vs. CNE1DDP and CNE2 vs. CNE2DDP). Gene Ontology, KEGG pathway, and miRNA analyses and protein-protein interactions of differentially expressed proteins showed that proteins TRIM29, HSPB1, CLIC1, ANXA1, and STMN1, among others, may play a role in the mechanisms of chemoresistance in clinical therapy. The chemotherapy-resistant proteomic profiles obtained may allow the identification of novel biomarkers for early detection of chemoresistance in NPC and other cancers.

PHP212 - Comparing Cost-Per-Qalys Gained And Cost-Per-Dalys Averted Analyses

We compared the literatures of two common metrics used in cost-effectiveness analyses: cost per quality-adjusted life years (QALYs) gained and cost per disability-adjusted life year (DALY) averted. We analyzed the Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry database, containing cost-per-QALY gained studies, and the Global Health CEA Registry database, containing cost-per-DALY averted studies. We documented differences in study characteristics – including intervention type, sponsor, country, and primary disease, and compared the number of available CEAs with regional burden of diseases. We identified 6,438 cost-per-QALY and 543 cost-per-DALY studies published through 2016 and observed rapid growth in publication rates for both literatures. Cost-per-QALY studies were most likely to examine pharmaceuticals and interventions in high-income countries. Cost-per-DALY studies predominantly focused on infectious disease interventions in low and lower-middle income countries. We found regional discrepancies in the number of published CEAs for diseases and conditions, suggesting “under-studied” areas (e.g., cardiovascular disease in Southeast Asia, East Asia, and Oceania) and “over-studied” areas (e.g., HIV in Sub Saharan Africa) relative to regional disease burden. The number of cost-per QALY and cost-per-DALY analyses has grown rapidly with applications to diverse interventions/diseases. Discrepancies between the number of published studies and disease burden suggest funding opportunities for future cost-effectiveness research.

The life cycle of non-polio enteroviruses and how to target it.

The genus Enterovirus (EV) of the family Picornaviridae includes poliovirus, coxsackieviruses, echoviruses, numbered enteroviruses and rhinoviruses. These diverse viruses cause a variety of diseases, including non-specific febrile illness, hand-foot-and-mouth disease, neonatal sepsis-like disease, encephalitis, paralysis and respiratory diseases. In recent years, several non-polio enteroviruses (NPEVs) have emerged as serious public health concerns. These include EV-A71, which has caused epidemics of hand-foot-and-mouth disease in Southeast Asia, and EV-D68, which recently caused a large outbreak of severe lower respiratory tract disease in North America. Infections with these viruses are associated with severe neurological complications. For decades, most research has focused on poliovirus, but in recent years, our knowledge of NPEVs has increased considerably. In this Review, we summarize recent insights from enterovirus research with a special emphasis on NPEVs. We discuss virion structures, host-receptor interactions, viral uncoating and the recent discovery of a universal enterovirus host factor that is involved in viral genome release. Moreover, we briefly explain the mechanisms of viral genome replication, virion assembly and virion release, and describe potential targets for antiviral therapy. We reflect on how these recent discoveries may help the development of antiviral therapies and vaccines.

Epidemic trend of scrub typhus in the world

Scrub typhus,infection with Orientia tsutsugamushi due to the bite by larvae of chigger mites,is an ancient vector-borne disease in Southeast Asia. During the World War Ⅱ,the disease occurred frequently in army in Southeast Asia and caused a lot of casualties,arousing great concern. After World War Ⅱ,reported scrub typhus cases gradually decreased, however,since 1980s,the incidence of scrub typhus has showed an upward trend,and the geographical distribution has also expanded. Currently,the incidence of scrub typhus is high in most traditional endemic counties in East Asia,South Asia, Southeast Asia and North Oceania(i.e. tsutsugamushi triangle). In recent years,scrub typhus cases and animal infection also emerged in Middle East,Africa,South America and even Europe. Given the increased incidence of scrub typhus in China,it is suggested to re-classified it as notifiable disease to reduce the disease burden in China.

A new extremely hazardous viral disease in southeast Asia which affects both swine and humans

Since the end of 1998, incidents of a serious viral encephalitis have been reported in Malaysia and recently in Singapore, a 50% of which led to death. According to the updated information on this new disease, its transmission is related to swine. At first, it was believed that cause of the encephalitis was the virus of the Japanese encephalitis type B. However, after the proper laboratory examinations, it was proved that a new, unknown virus was related to the etiology of the incidents. This virus belongs to the Paramyxoviridae family and has many common characteristics with the Hendra virus, without being the actual one. The first name attributed to the virus was Hendra like virus, but recently the name Nipah virus prevails.

Study of azithromycin sensitivity in enteric fever in pediatric population

Background: Enteric fever is a major human infectious disease in Southeast Asia. It is exacerbated by a high level of resistance some isolates display to the drugs routinely used in treatment. Azithromycin may be a treatment option for such isolates. Objective: The objective of this study was to analyze the azithromycin susceptibility in culture positive enteric fever and to evaluate the relationship between ciprofloxacin and azithromycin sensitivity and resistance patterns. Methods: This retrospective study was conducted at a tertiary care hospital, Bengaluru, India, between June 2012 and June 2016. Case records of 363 children in the age group of 0–18 years diagnosed with proven enteric fever were reviewed. Susceptibility to antimicrobial drugs was tested by the disc diffusion according to Kirby-Bauer method. They were interpreted based on Clinical and Laboratory Standards Institute guidelines 2016. Results: There were 280 Salmonella enterica serovar typhi (77.13%) and 83 serovar paratyphi A strains (22.86%) among the 363 enteric fever children. The susceptibility to azithromycin and third-generation cephalosporins has been 100% among these isolates. Azithromycin minimum inhibitory concentrations (MICs) were 0.064–12 ?g/ml among the 363 isolates, and there is no increase in resistance in the past 4 years. Only 5 (18.5%) of the isolates which were resistant to ciprofloxacin had MIC &gt;4 to azithromycin, but none were resistant to azithromycin. Conclusion: Salmonella typhi continues to remain susceptible to azithromycin and third-generation cephalosporins. There is no increasing trend in resistance to azithromycin over the years in the area of study. Azithromycin can be used in the isolates resistant to ciprofloxacin as there is no correlation between their resistances, thus making it a safe alternative for oral therapy of enteric fever in children.

Comparing the cost-per-QALYs gained and cost-per-DALYs averted literatures.

Background: We examined the similarities and differences between studies using two common metrics used in cost-effectiveness analyses (CEAs): cost per quality-adjusted life years (QALYs) gained and cost per disability-adjusted life year (DALY) averted. Methods: We used the Tufts Medical Center CEA Registry, which contains English-language cost-per-QALY gained studies, and Global Cost-Effectiveness Analysis (GHCEA) Registry, which contains cost-per-DALY averted studies. We examined study characteristics including intervention type, sponsor, country, and primary disease, and also analysed the number of CEAs versus disease burden estimates for major diseases and conditions across three geographic regions. Results: We identified 6,438 cost-per-QALY and 543 cost-per-DALY studies published through 2016 and observed rapid growth in publication rates for both literatures. Cost-per-QALY studies were most likely to examine pharmaceuticals and interventions in high-income countries. Cost-per-DALY studies predominantly focused on infectious disease interventions and interventions in low and lower-middle income countries. We found discrepancies in the number of published CEAs for certain diseases and conditions in certain regions, suggesting "under-studied" areas (e.g., cardiovascular disease in Southeast Asia, East Asia, and Oceania and "overstudied" areas (e.g., HIV in Sub Saharan Africa) relative to disease burden in those regions. Conclusions: The number of cost-per QALY and cost-per-DALY analyses has grown rapidly with applications to diverse interventions and diseases. Discrepancies between the number of published studies and disease burden suggest funding opportunities for future cost-effectiveness research.

SEI-model for transmission of Nipah virus

Nipah virus (NiV) has drawn attention as an emerging infectious disease in Southeast Asia. It has become one of the most alarming threats of the public health mainly due to its periodic outbreaks and the high mortality rate. In the present work, the transmission of NiV using SEI-model is analysed through the system of non-linear differential equations. In addition, the reproduction number is attained which signifies the intensity of NiV outbreak. The local and global stability of equilibrium points is studied. Numerical simulation illustrates the behavior and flow of NiV infections in different compartments.

SEI-model for transmission of Nipah virus

Nipah virus (NiV) has drawn attention as an emerging infectious disease in Southeast Asia. It has become one of the most alarming threats of the public health mainly due to its periodic outbreaks and the high mortality rate. In the present work, the transmission of NiV using SEI-model is analysed through the system of non-linear differential equations. In addition, the reproduction number is attained which signifies the intensity of NiV outbreak. The local and global stability of equilibrium points is studied. Numerical simulation illustrates the behavior and flow of NiV infections in different compartments.

Phytochemical profile of Orthosiphon aristatus extracts after storage: Rosmarinic acid and other caffeic acid derivatives

BackgroundOrthosiphon aristatus (Blume) Miq. is a medicinal herb which is traditionally used for the treatment of diabetes and kidney diseases in South East Asia. Previous studies reported higher concentration of antioxidative phytochemicals, especially rosmarinic acid (ester of caffeic acid) and other caffeic acid derivatives in this plant extract than the other herbs such as rosemary and sage which are usually used as raw materials to produce rosmarinic acid supplement in the market. PurposeThe phytochemical profile of O. aristatus was investigated at different storage durations for quality comparison. MethodsThe phytochemicals were extracted from the leaves and stems of O. aristatus using a reflux reactor. The extracts were examined for total phenolic and flavonoid contents, as well as their antioxidant capacities, in terms of radical scavenging, metal chelating and reducing power. The phytochemical profiles were also analyzed by unsupervised principal component analysis and hierarchical cluster analysis, in relation to the factor of storage at 4 °C for 5 weeks. ResultsThe leaf extract was likely to have more phytochemicals than stem extract, particularly caffeic acid derivatives including glycosylated and alkylated caffeic acids. This explains higher ratio of total phenolic content to total flavonoid content with higher antioxidant capacities for the leaf extracts. Rosmarinic acid dimer and salvianolic acid B appeared to be the major constituents, possibly contributing to the previously reported pharmacological properties. However, the phytochemical profiles were found changing, even though the extracts were stored in the refrigerator (4 °C). The change was significantly observed at the fifth week based on the statistical pattern recognition technique. ConclusionO. aristatus could be a promising source of rosmarinic acid and its dimer, as well as salvianolic acid B with remarkably antioxidant properties. The phytochemical profile was at least stable for a month stored at 4 °C. It is likely to be a good choice of herbal tea with comparable radical scavenging activity, but lower caffeine content than other tea samples.

Comparison of in-house IgM and IgG ELISAs for the serodiagnosis of melioidosis in Malaysia.

Melioidosis is an endemic infectious disease in Southeast Asia and northern Australia, caused by Burkholderia pseudomallei. However, the incidence rate in Malaysia is not well documented. The high mortality rate and broad range of clinical presentations require rapid and accurate diagnosis for appropriate treatment. This study compared the efficacy of in-house IgM and IgG ELISA methods using a local B. pseudomallei strain. The diagnostic accuracy of the in-house IgG ELISA was better than that of the IgM ELISA: sensitivity (IgG: 84.71 %, IgM: 76.14 %) and specificity (IgG: 93.64 %, IgM: 90.17 %); positive predictive value (IgG: 86.75 %, IgM: 79.76 %) and negative predictive value (IgG: 92.57 %, IgM: 89.66 %); likelihood ratio (LR) [IgG: 13.32, IgM: 7.75 (LR+); IgG: 0.16, IgM: 0.26 (LR–)], and was supported by the observation of the absorbance value in comparisons between culture and serology sampling. In-house IgG ELISA was shown to be useful as an early diagnostic tool for melioidosis.

Practice of iron chelation therapy for transfusion-dependent thalassemia in Southeast Asia

Background: Thalassemia is a common monogenic disease in Southeast Asia. Patients with transfusiondependent thalassemia require frequent blood transfusions, which can lead to iron overload and subsequent organ dysfunction and damage. Iron overload is avoided by chelation therapy. There are 3 types of chelatorsavailable for iron chelation therapy, namely, desferrioxamine, deferiprone, and deferasirox. Although practical guidelines are available for the management of transfusion-dependent thalassemia, not all countries are able to provide treatment for their patients. Objectives: To discuss the scope of iron chelation practices including the types of chelators that are available in Southeast Asia, and explore issues relevant to the treatment of transfusion-dependent thalassemic patients in this region. Methods: A literature search for information pertaining to thalassemia and its management from 2000 to 2015 was conducted using the following websites: PubMed/MEDLINE, Google Scholar, Scopus, and SpringerLink. Results: Not all Southeast Asian countries have yet published detailed information about their iron chelation practice and not all countries in Southeast Asia have uniform practices for thalassemia management based on published recommendations. Conclusions: Advances in treatment have improved the management of thalassemic patients. However, because of various issues, not all countries are able to provide an ideal treatment for their patients. Southeast Asian countries should work together to prevent this inherited disease. Keywords: Iron chelation therapy, practice, Southeast Asia, thalassemia

Working towards consensus: the need for coordinated policies to assist control of foot and mouth disease and emerging disease threats in South-East Asia.

Foot and mouth disease (FMD) is an important transboundary disease in South-East Asia. Its control has been a priority in the region for at least 20 years, with extensive institutional support and capacity-building being provided by the international community through the World Organisation for Animal Health. This paper describes the FMD control and eradication programme in the Mekong region (Myanmar, Thailand, the Lao People's Democratic Republic, Cambodia and Vietnam) of South-East Asia and evaluates the FMD control programme in one of the region's countries, namely Cambodia. Significant progress has been made, and the strategy for eradication is now both clearly understood and feasible in the Mekong. However, FMD control in this region requires more than just an effective vaccination strategy and regulatory support. Success will also depend on obtaining consensus and buy-in at all levels of the value chain, from input suppliers to consumers. Culturally and economically acceptable incentives must be in place to ensure that control measures are implemented, and those stakeholders who are expected to bear the risk and costs of control programmes must also be the main beneficiaries. The present institutional environment in the Mekong, and in particular in Cambodia, makes control and eradication of transboundary diseases difficult. Further work is required to ensure that control strategies are aligned with stakeholder needs and priorities, and actively improve smallholder welfare. Cattle producers and traders are crucial to the control of FMD in Cambodia. Economic incentives and education as well as regulation are required to ensure these stakeholders participate in this important transboundary disease eradication programme.

An Unusual Hydrops Fetalis Associated with Compound Heterozygosity for Krüppel-like Factor 1 mutations

Hydrops fetalis is commonly due to Hb Bart’s (γ4) disease in South East Asia. Here, we report an unusual case of hydrops fetalis due to congenital dyserythropoietic anemia (CDA) associated with compound heterozygosity for Krüppel-like factor 1 (KLF1) gene mutations. Fetal cardiomegaly was first detected on routine mid-trimester scan in a pregnant woman with normal mean corpuscular volume (MCV) and Rhesus positive status. The fetus subsequently developed hydrops fetalis, and cordocentesis showed severe fetal anemia with a hemoglobin (Hb) level of 3.4 g/dL. Common causes of fetal anemia including Hb Bart’s disease, parvovirus infection, and red cell antibodies were excluded. In view of the marked increase in erythroblasts at various stages of erythropoiesis, the diagnosis of CDA was suspected. We screened the couple for previously reported KLF1 gene mutations, showing that the mother was heterozygous for the c.525_526insCGGCGCC, p.Gly176Argfs*179 mutation, and her husband heterozygous for c.1012C>A, p.Pro338Thr mutation. The fetus was a compound heterozygote for these two KLF1 mutations. After counseling, repeated intrauterine transfusions were given at 27, 29, and 34 weeks’ gestation; the hydrops fetalis was resolved. The baby was delivered at 34 weeks’ gestation and required monthly blood transfusions but was otherwise thriving. Bone marrow aspiration at 10 months of age showed the features of ineffective erythropoiesis, compatible with CDA. In conclusion, hydrops fetalis can rarely be due to CDA associated with a compound heterozygous mutation for KLF1 gene mutations, and be managed by repeated intrauterine transfusions. Our present report adds to the wide clinical spectrum of KLF1 mutations.

Development of a checklist (I-SEAVD) for public health nutrition programmes related to cardiovascular disease in Southeast Asia

• Nutrition and health surveys in Southeast Asia allow surveillance of the diet and health status of their populations.

Burkholderia pseudomallei rpoS mediates iNOS suppression in human hepatocyte (HC04) cells.

Burkholderia pseudomallei is an intracellular Gram-negative bacterial pathogen and the causative agent of melioidosis, a widespread disease in Southeast Asia. Reactive nitrogen, in an intermediate form of nitric oxide (NO), is one of the first lines of defense used by host cells to eliminate intracellular pathogens, through the stimulation of inducible nitric oxide synthase (iNOS). Studies in phagocytotic cells have shown that the iNOS response is muted in B. pseudomallei infection, and implicated the rpoS sigma factor as a key regulatory factor mediating suppression. The liver is a main visceral organ affected by B. pseudomallei, and there is little knowledge about the interaction of liver cells and B. pseudomallei. This study investigated the induction of iNOS, as well as autophagic flux and light-chain 3 (LC3) localization in human liver (HC04) cells in response to infection with B. pseudomallei and its rpoS deficient mutant. Results showed that the rpoS mutant was unable to suppress iNOS induction and that the mutant showed less induction of autophagy and lower co-localization with LC3, and this was coupled with a lower intracellular growth rate. Combining these results suggest that B. pseudomallei rpoS is an important factor in establishing infection in liver cells.

The current status of Zika virus in Southeast Asia.

OBJECTIVES:Zika virus currently poses a global threat and is a major public health issue throughout Latin America and the Caribbean. However, Zika virus infections in humans have also been observed in other regions, including Southeast Asia, where arboviral diseases are very common. In this study, we summarize the current status of Zika virus in Southeast Asia. This review aims to provide an overview of the current situation and also to suggest ways of adequately managing the emergence of Zika virus in Southeast Asia.METHODS:The literature searching for the reports on Zika virus in Southeast Asia was done using standard database PubMed and the re-analysis and summarization on the reports was done.RESULTS:A limited number of reports have addressed Zika virus disease in Southeast Asia, but it is has been confirmed that a problem already exists. Individual case reports and outbreaks of Zika virus have been confirmed in Southeast Asia. Several reports have also described patients becoming infected after visiting Southeast Asia. In addition, the concurrent circulation of Zika virus with other arboviruses has been confirmed.CONCLUSIONS:As a tropical region with a high prevalence of arboviral diseases, the emergence of Zika virus in Southeast Asia is a major concern. It is essential for local medical personnel to recognize this disease. Given the status of Southeast Asia as a globally important tourist destination, continuous updates on the status of Zika virus in Southeast Asia are required and should be incorporated into global health advisories regarding travel.

Assessing the role of landscape connectivity on Opisthorchis viverrini transmission dynamics

Opisthorchis viverrini (Ov) is one of the most important human parasitic diseases in Southeast Asia. Although the concept of connectivity is widely used to comprehend disease dispersal, knowledge of the influences of landscape connectivity on Ov transmission is still rudimentary. This study aimed to investigate the role of landscape connectivity in Ov transmission between the human and the first intermediate snail hosts. Fieldwork was conducted in three villages respectively in Kamalasai District, Kalasin Province, Phu Wiang District, Khon Kaen Province, and Nong Saeng District, Udon Thani Province. Bithynia snails were collected to examine parasitic infections, water samples were analyzed for fecal contamination, and locations of septic tanks and connections between habitat patches with observable water movement were surveyed. Euclidean distance, topological link and distance, and graph measures were employed to quantify the connectivity between human and snail habitats. The findings showed that snail patches with higher fecal contents were generally located nearer to septic tanks. The statistically significant results for the topological link and distance measures highlighted the importance of water in functionally facilitating Ov transmission. Graph measures revealed differences in landscape connectivity across the sites. The site with the largest landscape component size and the most mutually connected snail patches coincided with the presence of Ov parasite, reinforcing its higher risk for human to snail transmission. The site with the dissected landscape structure potentially limited the transmission. This study underscored the potential effect of landscape connectivity on Ov transmission, contributing to the understanding of the spatial variation of Ov infection risk.