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DNA vaccine constructs against enterovirus 71 elicit immune response in mice

Tung WS, Bakar SA, Sekawi Z, Rosli R

Genet Vaccines Ther, 2007;5:6.
PMID: 17445254

Enterovirus 71 (EV71) is a major causative viral agent responsible for large outbreaks of hand, foot and mouth disease (HFMD), a common rash illness in children and infants. There is no effective antiviral treatment for severe EV71 infections and no vaccine is available. The objectives of this study were to design and construct a DNA vaccine against Enterovirus 71 using the viral capsid protein (VP1) gene of EV71 and to verify the functionality of the DNA vaccine in vitro and in vivo.
Association between IL-10 gene polymorphisms (- 1082 A/G, -819 T/C, -592 A/C) and hepatocellular carcinoma: a meta-analysis and trial sequential analysis

Mei TTY, Aung HH, Tung WS, Naing C

BMC Cancer, 2023 Sep 08;23(1):842.
PMID: 37684564 DOI: 10.1186/s12885-023-11323-1

BACKGROUND: The carcinogenesis of hepatocellular carcinoma is complicated, and genetic factor may have the role in the malignant transformation of liver cells. IL-10 gene polymorphisms have been investigated for their potential roles in hepatocellular carcinoma This study aimed to investigate the relationship between polymorphisms of IL-10 (-1082 A/G, -819 T/C, -592 A/C), and hepatocellular carcinoma by performing a meta-analysis with eligible individual studies.
METHODS: This study followed the PRISMA 2020 Checklist. Relevant studies were searched in health-related databases. The Newcastle-Ottawa Scale criteria were used to evaluate the studies quality. Pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and hepatocellular carcinoma using five genetic models. Stratification was done by ethnic groups. Trial sequential analysis (TSA) was performed to determine the required information size.
RESULTS: Fifteen case-control studies (n = 8182) were identified. Overall, the heterozygous model showed a marginal significant association only between IL-10 (-1082 A/G) and hepatocellular carcinoma risk (OR: 0.82, 95% CI: 0.67-1.00, 9 studies). On stratification, IL-10 (-1082 A/G) was significantly associated with hepatocellular carcinoma risk in the non-Asian population under dominant (OR: 0.62, 95% CI: 0.45-0.86, 4 studies), heterozygous (OR: 0.60, 95% CI: 0.43-0.85) and allelic models (OR: 0.79, 95% CI: 0.64-0.99). IL-10 (-819 T/C) was significantly associated with hepatocellular carcinoma risk only among non-Asians under the dominant (OR: 1.47, 95% CI: 1.02-2.13, 8 studies), recessive (OR: 1.99, 95% CI: 1.03-3.86, and homozygous models (OR: 2.18, 95% CI: 1.13-4.23). For IL-10 (-592 A/C) with 11 studies, there was no significant association with hepatocellular carcinoma in all five genetic models (P values > 0.5). TSA plots indicated that the information size for firm evidence of effect was sufficient only for the analysis of IL-10 (-592 A/C), but not for the - 1082 A/G or -819 T/C.
CONCLUSIONS: Findings suggest that IL-10 (-1082 A/G and - 819 T/C) polymorphisms are associated with hepatocellular carcinoma in ethnic-specific manner. However, this evidence is not conclusive because the sample size was insufficient. IL-10 (-592 A/C) polymorphism was not associated with hepatocellular carcinoma albeit with sufficient information size. Future well-designed large case-control studies on IL-10 (-1082 A/G and - 819 T/C) with different ethnicities are recommended.
Rapid diagnostic test (Leptocheck-WB) for detection of acute leptospirosis: a meta-analysis of diagnostic accuracy

Hwee SE, Htet NH, Naing C, Tung WS, Mak JW

Eur J Clin Microbiol Infect Dis, 2022 Feb 11.
PMID: 35147814 DOI: 10.1007/s10096-022-04420-9

The majority of leptospirosis is subclinical or mild self-limiting systemic illness. A rapid and accurate diagnostic test for the detection of leptospirosis is essential to prevent disease progression from acute non-severe illness to potentially fatal infection. Rapid diagnostic tests (RDTs) recognized as point-of-care (PoC) tests may support clinical decision-making in resource-poor settings. We aimed to assess the accuracy of PoC (Leptocheck-WB) for the detection of acute leptospirosis by meta-analysis of data from eligible studies. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guideline. The pooling of data was done only when there were two or more studies that used a particular type of reference test. A total of ten studies (n = 5369) were identified. The majority (70%) were from the Asian region. Using microscopic agglutination test (MAT) as reference test, the pooled sensitivity (0.75, 95% CI: 0.64 to 0.84, 10 studies, I2: 85.9%) and specificity (0.87, 95% CI: 0.77 to 0.94, 10 studies, I2: 97.37%) of Leptocheck-WB in the detection of leptospirosis were moderate. With the use of enzyme-linked immunosorbent assay (ELISA) reference test, the pooled sensitivity 0.85 (95% CI: 0.79 to 0.9, 4 studies, I2: 27.49%) and specificity 0.79 (95% CI: 0.71 to 0.85, 4 studies, I2: 58.9%) of Leptocheck-WB were also moderate. Diagnostic odds ratio of Leptocheck-WB with MAT (21, 95% CI: 10-44) or with ELISA as reference test (21, 95% CI: 9-46) showed an acceptable level of accuracy. Meta-regression analysis showed methodological quality of studies (p: 0.06) and study design (p: 0.09) were potential factors that affected the accuracy of Leptocheck-WB test. Findings suggest that Leptocheck-WB has a moderate level of acceptance for detection of acute leptospirosis. Further confirmation with large-sampled, prospectively designed studies using the same samples for evaluating test accuracy is recommended.
Loop-mediated isothermal amplification (LAMP) test in the detection of uncomplicated malaria in pregnancy: a meta-analysis of diagnostic accuracy

Yon JLT, Htet NH, Naing C, Tung WS, Aung HH, Mak JW

Malar J, 2022 Dec 22;21(1):391.
PMID: 36550507 DOI: 10.1186/s12936-022-04419-9

BACKGROUND: Due to relatively low malaria parasitaemia in pregnancy, an appropriate field test that can adequately detect infections in pregnant women presenting with illness or for malaria screening during antenatal care is crucially important. The objective was to evaluate the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for the detection of uncomplicated malaria in pregnancy.
METHODS: This was a meta-analysis of diagnostic accuracy. Relevant studies that assessed the diagnostic performance of LAMP for the detection of malaria in pregnancy were searched in health-related electronic databases including PubMed, Ovid, and Google Scholar. The methodological quality of the studies included was evaluated using the QUADAS-2 tool.
RESULTS: Of the 372 studies identified, eight studies involving 2999 pregnant women in five endemic countries that assessed the accuracy of LAMP were identified. With three types of PCR as reference tests, the pooled sensitivity of LAMP was 91% (95%CI 67-98%) and pooled specificity was 99% (95%CI 83-100%, 4 studies), and the negative likelihood ratio was 9% (2-40%). Caution is needed in the interpretation as there was substantial between-study heterogeneity (I2: 80%), and a low probability that a person without infection is tested negative. With microscopy as a reference, the pooled sensitivity of LAMP was 95% (95%CI 26-100%) and pooled specificity was 100% (95%CI 94-100%, 4 studies). There was a wide range of sensitivity and substantial between-study heterogeneity (I2: 83.5-98.4%). To investigate the source of heterogeneity, a meta-regression analysis was performed with covariates. Of these potential confounding factors, reference test (p: 0.03) and study design (p:0.03) had affected the diagnostic accuracy of LAMP in malaria in pregnancy. Overall, there was a low certainty of the evidence in accuracy estimates.
CONCLUSION: The findings suggest that LAMP is more sensitive than traditional tests used at facilities, but the utility of detecting and treating these low-density infections is not well understood. Due to the limited number of studies with bias in their methodological quality, variation in the study design, and different types of reference tests further research is likely to change the estimate. Well-conceived large prospective studies with blinding of the index test results are recommenced.
Fulltext Community engagement in health services research on soil-transmitted helminthiasis in Asia Pacific region: Systematic review

Naing C, Tung WS, Htet NH, Aung HH, Whittaker MA

PLOS Glob Public Health, 2023;3(3):e0001694.
PMID: 36963099 DOI: 10.1371/journal.pgph.0001694

The research question was what studies are available that have assessed community engagement in the health services research on soil-transmitted helminths? We aimed to synthesise evidence on how communities were engaged in health services research on soil-transmitted helminths in low-and-middle-income countries of the Asia-Pacific Region. We focused on this region because soil-transmitted helminths are endemic, and their burden is significant in this region. This review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) checklist. Relevant studies were searched in health-related databases including PubMed, Ovid, and Google Scholar. We selected studies based on the selection criteria set for this review. We collected textual information about the type of health services research, the degree of community engagement, the research phases involved, and the barriers/enablers affecting community engagement in research since they are pertinent to our review question and objective. Ten studies from seven countries in the Asia Pacific region were identified for this review. Albeit with variation in the extent of their involvement, various forms of communities/groups within communities were included such as Aboriginal communities, local communities, school children and their parents, school teachers and headmasters of schools, heads of villages, religious leaders, and so on. Overall, community engagement in health services research focused on of soil-transmitted helminths was limited. Six studies (60%) had collaboration at 'developing methodology', mainly through an explanation of the objectives of the study or study process to be conducted. Seven studies (70%) revealed community participation in soil-transmitted helminths at the "data collection" stage. Only one study (10%) documented that a community leader was involved as a co-author, reflecting an involvement in 'report writing' and further 'dissemination'. Findings suggest that there were various forms of community engagement in various aspects of the health services research context. Overall, there was moderate level of participation, but there was insufficient information on the partnership between various stakeholders, which prevented in-depth analysis of the engagement. Future health services research on soil-transmitted helminth interventions needs to be carefully planned, well designed, grounded in principles of community engagement, and designed methodologically to allow in-depth participation by communities in all stages of the research.
Toll-like receptor 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer: a meta-analysis of genetic association studies

Qyi YZ, Aung HH, Aye SN, Tung WS, Naing C

BMC Cancer, 2023 Oct 24;23(1):1027.
PMID: 37875868 DOI: 10.1186/s12885-023-11509-7

BACKGROUND: Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies.
METHODS: This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed.
RESULTS: Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90-1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38-4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74-2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07-1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12-11.76, I2 = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76-2.86, I2 = 82%; Asian: OR = 1.54, 95% CI = 1.13-2.1, I2 = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I2 = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89-1.71, I2 = 84%; Asian: OR = 1.22, 95% CI = 1.05-1.41, I2 = 0%; non-Asian: OR = 1.24, 95% CI = 0.34-4.59, I2 = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions.
CONCLUSIONS: The findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.
Prevalence of zoonotic (brugian) filariasis in Asia: A proportional meta-analysis

Whittaker MA, Naing C, Tung WS, Aung HH, Wah MJ

Acta Trop, 2023 Oct 20.
PMID: 37866729 DOI: 10.1016/j.actatropica.2023.107049

Lymphatic filariasis is a public health problem and targeted for global elimination. WHO recommends mass drug administration to interrupt transmission of the parasites involved. There are concerns that transmission interruption may be difficult in areas of zoonotic filarial infections. This study aimed to estimate the pooled prevalence of zoonotic brugian filariasis, and to compare the pooled prevalence of brugian filariasis in human and animal populations in the same area based on available studies. A comprehensive literature search was conducted in health-related electronic databases (PubMed, Ovid MEDLINE, Index Medicus, google scholar). A random-effect meta-analysis of the pooled overall prevalence of filariasis in animal populations was conducted. Sixteen studies from four different Asian countries were identified. Studies were conducted most frequently in Thailand (n = 7), followed by Malaysia (n = 5), India (n = 3), and Sri Lanka (n = 1). Regardless of animal group, the pooled overall prevalence of animal Brugia infections was 13% (95%CI: 7-21%, I2:98%, 16 studies). On stratification, the pooled overall prevalence in the animal population was 19% (95%CI: 1-50%, I2: 99%, 3 studies) in India, 8% (95%CI: 2-7%, I2: 97%, 5 studies) in Malaysia, and 13% (95%CI: 7-20%, I2: 94%, 7 studies) in Thailand. The prevalence in the animal population was 17% (95%CI: 13-21%, 1 study) in Sri Lanka. The pooled overall prevalence of Brugia malayi was 13% (95%CI: 7-21%, I2:98%, 12 studies), while for Brugia pahangi this was 12% (95%CI: 7-19%, I2:86%, 7 studies). Regardless of animal group, geographic area, or diagnostic test, the prevalence of B. malayi was consistently high. On stratification by animal category, the pooled overall prevalence was 10% (95%CI: 6-14%, I2:92%, 13 studies) in cats, 12% (95%CI: 2-28%, I2: 99%, 6 studies) in dogs, and 55% (95%CI: 47-63%, 1 study) in leaf-eating monkeys. The findings show the extent of zoonotic Brugiainfections in domestic cats and dogs, suggesting that these animals are potential reservoirs for human brugian filariasis in the study countries. To substantiate this with more accuracy, future well designed whole genomic sequencing of individual mf collected from humans and B. malayi infected animals in the same area are needed.
Fulltext Facilitators and barriers to engaging communities in health service research on dengue control in Indo-Pacific region: a systematic review

Naing C, Htet NH, Tung WS, Aung HH, Whittaker MA

BMC Public Health, 2023 Oct 05;23(1):1924.
PMID: 37798703 DOI: 10.1186/s12889-023-16845-8

BACKGROUND: Dengue is a public health problem in the Indo-Pacific countries. There are concerns over the facilitators and barriers to community engagement in health service research aimed at dengue control. The objective of his study was to identify and synthesize facilitators and barriers to community engagement in health service research aimed at dengue control.
METHODOLOGY: The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) checklist was used to perform this review. Health-related databases including PubMed, Ovid, and Google Scholar were searched for relevant studies. A consolidated framework with five domains was developed after undertaking a six-phase reflective thematic assessment of the data.
RESULTS: Thirteen studies were identified, spanning eight low-and middle-income countries of the Indo-Pacific region including Cambodia, India, Indonesia, Myanmar, Philippines, Sri Lanka, Thailand, and Vietnam. The studies in this review covered the period from 2002 to 2021. A broad range of study designs and objectives were revealed across these 13 studies. An array of communities such as the local government, project-related health staff, local health services staff, community leaders, local communities/residences/general public, heads of households, community health volunteers, school teachers, and schoolchildren participated in these dengue related studies. The five Consolidated Framework for Implementation Research (CFIR) domains of 'intervention characteristics', 'inner setting', 'outer setting',' individual characteristics', and 'program implementations' were used to identify and describe barriers and facilitators.
CONCLUSIONS: The findings indicate a range of barriers and facilitators to community engagement in dengue control in the selected LMIC in the Indo-Pacific countries. Future health services research on dengue control approaches should be carefully planned, methodologically constructed, aligned with community engagement principles, and involve considerable community participation at all stages of the research.